| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The University of Iowa Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242, USA; and
* Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA
1Correspondence: Department of Ophthalmology and Visual Sciences, The University of Iowa, 11190E PFP, 200 Hawkins Dr., Iowa City, Iowa 52240, USA. E-mail address: gregory-hageman{at}uiowa.edu
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
Key Words: retina • retinal pigmented epithelium • amyloid • vitronectin • soft drusen
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
2
3
4
5
6
7
8)
. Early clinical signs of AMD include pigmentary
changes at the level of the retinal pigmented epithelium (RPE) and an
accumulation of abnormal extracellular deposits, called drusen,
adjacent to the basal surface of the RPE. Histologically, drusen are
located between the basal lamina of the RPE and the inner collagenous
layer of Bruch’s membrane (9
10
11
12)
. Drusen size, number,
and degree of confluence are significant risk factors for the
development of AMD (9
, 11)
. It has been proposed that
drusen, as well as other age-related changes that can occur in the
vicinity of Bruch’s membrane, may lead to dysfunction and/or
degeneration of the RPE and retina by inducing ischemia and/or by
restricting the exchange of nutrients and waste products between the
neural retina and choroid (13)
. In addition, drusen
themselves may have a detrimental effect on vision, particularly with
respect to contrast sensitivity (14
15
16
17
18)
. Significantly, a
few recent studies have shown that laser photocoagulation treatment of
soft drusen can elicit drusen regression and, in some cases,
improvement of visual acuity (19
20
21
22
23)
.
In view of the strong correlation between drusen deposition and the
development of AMD, a more thorough understanding of drusen composition
and origin is likely to provide new insight into the pathobiology of
this disease. Comprehensive data pertaining to drusen composition and
to potential compositional differences between drusen phenotypes are
lacking. The few histochemical and immunohistochemical studies
(24
25
26
27
28
29
30
31)
of drusen that have been performed frequently
used small numbers of human donor eyes often with long postmortem
times, did not consider potential compositional differences between
drusen phenotypes, used relatively few probes, did not typically
consider the effects of tissue processing on drusen composition, and in
some cases provided conflicting data.
We recently identified vitronectin, a multifunctional plasma and
extracellular matrix protein, as a major component of drusen
(32)
. Vitronectin is a multifunctional glycoprotein that
participates in cell adhesion, maintenance of hemostasis, and
inhibition of complement-induced cell lysis (33)
.
Vitronectin is also a component of pathological extracellular
deposits associated with atherosclerosis (34
, 35)
,
amyloidosis (36)
, elastosis (37)
, and dense
deposit disease associated with membranoproliferative
glomerulonephritis type II (38)
. Like drusen, all of these
deposits form within the extracellular matrix and are associated with
advancing age. One epidemiological study has provided data suggesting a
strong correlation between advanced AMD and atherosclerosis of carotid
arteries (39)
, while another identified a significant
correlation between elastotic degeneration of nonsolar-exposed dermis
and choroidal neovascularization in AMD patients (40)
.
Based on these data, one can speculate that these diseases may share
similar genetic/environmental risk factors, developmental pathways,
and/or etiologies.
In this study, we demonstrate that there is a high degree of compositional similarity between ocular drusen and the extracellular deposits characteristic of other age-related diseases. We used information pertaining to the established compositions of amyloid deposits, elastotic plaques, atherosclerotic plaques, and dense deposits as a baseline to further refine our understanding of drusen composition and to assess the degree of similarity between drusen and these pathological deposits. The results provide additional insight into drusen composition and the pathobiology of AMD.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
.
Tissues from a minimum of five donors (at least two of whom had
clinically documented AMD) were assayed with each antibody used, and
each drusen phenotype was examined in at least two donors.
Institutional Review Board committee approval for the use of human
donor tissues was obtained from the Human Subjects Committee at The
University of Iowa.
Immunohistochemistry
Posterior poles, or wedges of posterior poles spanning between
the ora serrata and macula, were fixed in 4% (para)formaldehyde in
100 mM sodium cacodylate, pH 7.4. After 2–4 h of fixation, eyes were
transferred to 100 mM sodium cacodylate and rinsed (3x10 min),
infiltrated, and embedded in acrylamide, as described previously
(41)
. These tissues were subsequently embedded in OCT,
snap frozen in liquid nitrogen, and stored at -80°C. Unfixed
posterior poles or wedges thereof were embedded directly in OCT,
without acrylamide infiltration or embedment. Both fixed and unfixed
tissues were sectioned to a thickness of 6–8 µm on a cryostat. The
presence and type(s) of drusen were documented on adjacent sections
stained with hematoxylin/eosin, periodic acid Schiff reagent, and Sudan
black B (1% in 70% ethanol).
Immunolabeling was performed as described previously (32)
.
Adjacent sections were incubated with secondary antibody alone to serve
as negative controls. Some immunolabeled specimens were viewed by
confocal laser scanning microscopy, as described previously
(42)
.
Antibodies were obtained from Accurate (Westbury, N.Y.), Boehringer
Mannheim (Indianapolis, Ind.), Calbiochem (La Jolla, Calif.), Chemicon
(Temecula, Calif.), Dako (Carpinteria, Calif.), StressGen
Biotechnologies (Victoria, B.C.), and ICN (Costa Mesa, Calif.)
(Table 1
). Since most of the antibodies used in this study react with serum
proteins, retinal antigens, and/or choroidal antigens, positive
controls for many of the antibodies were based on appropriate labeling
of these tissues. Other control tissues included human liver, cornea,
and ocular skeletal muscle, as appropriate.
|
Amyloid histochemistry
Sections containing hard and soft drusen phenotypes were stained
for amyloid with crystal violet (Allied Chemical; New York, N.Y.),
Congo red (Sigma Chemical; St. Louis, Mo.), and thioflavin T (Sigma)
using established protocols (43)
. Human liver and cornea
were used as a positive control tissue for amyloid staining.
Birefringence was assessed by viewing Congo red-stained sections under
polarized light. Thioflavin T-stained sections were examined using
ultraviolet fluorescence optics (Olympus UG-1 filter set).
Reverse transcription-polymerase chain reaction (RT-PCR) analyses
To determine whether drusen-associated molecules are synthesized
by local ocular sources, total RNA was isolated from neural retina,
RPE, or combined RPE and choroid using the RNeasy system (Qiagen;
Valencia, Calif.). Liver and peripheral blood leukocyte RNA, as well as
genomic DNA, served as positive and negative controls, respectively.
RT-PCR was performed as described previously (32)
. Primers
to nucleotide sequences of the 15 molecules examined in this study were
used to amplify cDNA molecules from these tissue sources. Primer
sequences are depicted in Table 2
. Reaction mix without template and/or omission of reverse transcriptase
during the RT reaction were used as negative controls. PCR
amplification products were separated by agarose gel electrophoresis
and stained with ethidium bromide for visualization.
|
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
were incubated with a battery of antibodies directed
against proteins known to be present in abnormal deposits associated
with amyloidosis, atherosclerosis, elastosis, and dense deposit
disease. Hard and soft drusen, and their respective subclasses, exhibit
nearly identical immunohistochemical reactions with the majority of
antibodies used (Table 1)
. All reactions were specific based on
positive reactivity with the appropriate control tissue (see Fig. 1
). All drusen phenotypes examined were bound by antibodies directed
against amyloid P component and apolipoprotein E (Fig. 1C, D
), two plasma proteins also present in abnormal extracellular
deposits associated with atherosclerosis and various amyloidoses
(45
46
47
48
49)
. These antibodies bound homogeneously to both
hard and soft drusen. The immunofluorescence associated with drusen was
consistently more intense than that of the adjacent choroid. Antibodies
directed against complement component C5 (Fig. 1A, B
), the
terminal C5b-9 complement complex, and Factor X also reacted
homogeneously with all classes of hard and soft drusen. Immunoglobulin
lambda chain and transthyretin (prealbumin) frequently bound
drusen, although this labeling was less consistent (~75% of donors:
9 of 13 and 9 of 12, respectively). This labeling did not correspond to
specific ultrastructural drusen phenotypes. Strong transthyretin
immunoreactivity was invariably noted in the RPE, however (Fig. 2A
).
|
|
Weak and/or inconsistent drusen labeling of antibodies directed against
the protease inhibitors 
1-antitrypsin and
1-antichymotrypsin was observed. Labeling with
complement C3c antibody was more variable than C5 antibody labeling;
strong choroidal immunoreactivity was consistently observed with
antibodies directed against C3c, whereas drusen reactivity ranged from
negative to strongly positive. Drusen that did not react with C3
antibodies, however, invariably exhibited C5 immunoreactivity in
adjacent tissue sections, as did all drusen phenotypes examined. Weak
or inconsistent immunoreactivity was also noted in some donors with
antibodies directed against amyloid A component, fibrin, immunoglobulin
kappa chain, cystatin C, apolipoprotein B, complement C1q, C-reactive
protein, and ß2-microglobulin (see examples of
negative reactions in Figs. 1
and 2
). Ubiquitin reactivity was noted in
small punctate regions of drusen in one donor, but typically was not
observed.
No reaction of antibodies to the primary amyloid proteins keratin,
apolipoprotein A-I, gelsolin, calcitonin, atrial natriuretic factor,
ß-peptide, tau, or amyloid precursor protein was observed (Table 1)
.
Antibodies directed against human serum albumin and haptoglobin bound
strongly to the choroidal stroma, but not to hard or soft drusen (Fig. 1
; see also ref 32
).
Immunoreactivity of some drusen-associated proteins was frequently
observed in distinct, heterogeneous patterns. For example, drusen
binding by prothrombin and amyloid A antibodies was often localized to
vesicular profiles within drusen (Fig. 1G, I
). Double
labeling of the same drusen with vitronectin (Fig. 1H
)
revealed that the localization of prothrombin and amyloid A is not an
artifact of condensation of drusen constituents. Drusen were labeled
occasionally by anti-fibrinogen antibodies (four of seven donors); this
binding was generally confined to peripheral regions and/or concentric
bands within drusen (Fig. 1F
). In one donor, this
labeling was confined to large drusen, whereas smaller drusen were
nonreactive.
In addition, strong immunoreactivity of drusen to two monoclonal
antibodies directed against human leukocyte antigen-DR (HLA-DR)
molecules was noted (Fig. 2C
). This labeling was often
confined to globular or core-like domains within drusen near the inner
collagenous zone (data not shown). This pattern of labeling is similar
to that described for peanut agglutinin after neuraminidase treatment
(50)
.
As has been described previously, some drusen stain pale red with Congo
red (28)
; this is also observed with amyloid deposits.
However, no drusen phenotype examined exhibits the characteristic apple
green birefringence of amyloids stained with Congo red when observed
under polarized light. Like amyloids, drusen stained with crystal
violet (although without obvious metachromasia) and under UV
illumination displayed an intense white fluorescence after staining
with thioflavin T (data not shown). Thioflavin T staining also revealed
amyloid-like material surrounding blood vessels in the inner retina of
some eyes.
Transmission electron microscopy
In ongoing ultrastructural studies (44)
we have
failed to identify any electron microscopic evidence of nonbranching,
10–15 nm diameter fibrils that are characteristic of amyloid deposits
in over 320 donors examined (data not shown). In an attempt to expose
drusen-associated fibrils that might be masked by lipids and/or
membranous debris, drusen-containing tissues were pretreated with DMSO,
chloroform/methanol/HCl, or urea/Nonidet P-40 prior to embedding and
sectioning. No fibrillar substructures were observed within drusen
after such treatments (data not shown).
RT-PCR
Ocular cells were identified as sources for transcripts encoding a
number of drusen-associated molecules (see Table 2
and Fig. 3
). The RPE contained appropriately sized PCR fragments for albumin,
alpha-1-antichymotrypsin, apolipoprotein E, complement C3, complement
C5, and HLA-DR. Neural retina and/or choroid possessed transcripts
coding for Factor X, apolipoproteins B and E, complement proteins C3,
C5, and C9, immunoglobulins kappa and lambda, HLA-DR, fibrinogen, and
albumin. It is likely that some of these transcripts are synthesized by
vascular retinal and/or choroidal leukocytes. Prothrombin and amyloid P
transcripts of the appropriate sizes were detected only in the liver,
suggesting that these drusen-associated proteins may be derived from
extraocular tissue.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
. Although surprisingly few of these antibodies
reacted with drusen, those directed against vitronectin reacted
intensely and consistently with all ultrastructural phenotypes of hard
and soft drusen (44)
.
Vitronectin is a known component of extracellular deposits associated
with nonocular, age-related diseases including atherosclerosis,
amyloidosis, dense deposit disease, and dermal elastotic degeneration
(see Table 3
; 35
, 37
, 38
, 51
). In view of the documented clinical
correlations between the incidence of AMD and that of atherosclerosis
(39)
and dermal elastotic degeneration (40)
,
we screened drusen with a second panel of antibodies directed against
molecules known to colocalize with vitronectin in pathological
extracellular matrix deposits associated with these extraocular
diseases. We also examined drusen for histochemical and ultrastructural
evidence of other features diagnostic for amyloid deposits. The results
revealed that both hard and soft drusen phenotypes contain additional
molecular species associated with abnormal deposits found in other
age-related diseases (Table 3)
.
|
Relationship between drusen and amyloid deposits
Histochemically, amyloid deposits are eosinophilic, metachromatic
after being stained with crystal violet, fluorescent after being
stained with thioflavin T, and birefringent under polarized light after
exposure to Congo red (52)
. Amyloid deposits
characteristically contain a fibrillar protein that exhibits a high
degree of antiparallel beta-sheet conformation, heparan sulfate
proteoglycans, and amyloid P component (45
, 53)
. Plaques
associated with Alzheimer’s disease contain amyloid ß,
apolipoprotein E, -1-chymotrypsin, immunoglobulin G (IgG),
complement proteins, amyloid P, glycosaminoglycans, and Sp40,40
(54)
.
Drusen share some of these histochemical and compositional properties,
but not others. They stain positively with crystal violet, thioflavin T
(see also ref 55
), and (to a lesser degree) with Congo
red, but do not exhibit metachromasia or emit green birefringence. In
addition, drusen are eosinophilic and show strong evidence of amyloid P
component immunoreactivity. Amyloid P is also a component of nonamyloid
deposits associated with atherosclerosis (34)
, keratin
intermediate filament aggregates (56)
, and dense deposits
characteristic of glomerulonephropathy (47)
. Amyloid P
component associates with elastic fibers, where it may function as a
protease inhibitor (57)
. This protein is also a normal
component of Bruch’s membrane, where it may protect the elastic lamina
against enzymatic degradation (58)
. It is possible that
the accumulation of amyloid P, TIMP3 (59)
and, less
frequently, 1-antichymotrypsin (an inhibitor
of serine proteases) in drusen may act to counterbalance attempts by
RPE or choroidal cells to clear drusen proteolytically. Whether or not
sulfated proteoglycans, ubiquitous components of amyloids, are present
in drusen remains to be firmly established (27
, 30)
,
although we have identified weak reaction of heparan sulfate antibodies
with some drusen (32)
.
Although one investigation has reported a reaction of drusen with
monoclonal antibodies directed against ß-peptide (28)
, a
principal component of cerebral amyloid in Alzheimer’s disease, we did
not detect immunoreactivity for ß-peptide or its parent molecule,
amyloid precursor protein, in drusen. We did, however, identify a
number of molecules that serve as precursors for amyloid fibrils as
components of drusen in some eyes. These include transthyretin,
immunoglobulin light chains, and amyloid A. Other known precursors of
amyloid fibrils, including ß2-microglobulin, apolipoprotein A1,
atrial natriuretic factor, calcitonin, gelsolin, or cystatin C, were
not detected as components of drusen. Furthermore, ultrastructural
analyses of drusen do not reveal any classic, nonbranching, 10–15 nm
diameter amyloid fibrils within drusen even after pretreatment of
tissues with lipid-solubilizing compounds.
On balance, our evidence strongly suggests that although drusen exhibit
some of the characteristics of amyloid and contain several
amyloid-associated proteins, they do not contain fibrils characteristic
of true amyloids. Thus, drusen do not appear to be an ocular
manifestation of any of the identified forms of amyloidoses, nor do
they appear to be an ocular-specific form of amyloidosis. There are
certainly alternative explanations for the presence of
amyloid-associated molecules in drusen. For example, since
transthyretin is the major carrier of vitamin A in the blood, its
accumulation in some drusen could result from decreased permeability
between the choroid and RPE. It is intriguing to speculate that the
accumulation of transthyretin that sometimes occurs in drusen and other
sub-RPE deposits might result in a reduction of available vitamin A to
the RPE/retina, ultimately leading to the photoreceptor/RPE cell
degeneration observed in AMD. Alternatively, since transthyretin has
been reported to be synthesized by RPE cells (60)
, its
presence in some drusen might support hypotheses suggesting that drusen
originate from RPE cells (61)
.
Relationship between drusen and elastotic lesions
Elastosis is a heterogeneous group of disease conditions in which
the elastic fibers in the dermis undergo hyperplasia and/or
rearrangement. Whereas sun-exposed skin typically develops elastotic
lesions by the second decade of life, these accumulations are less
common and severe in sun-protected areas of the skin (62)
.
The presence of elastotic degeneration of sun-protected dermis has been
shown to correlate with the incidence of neovascular AMD
(40)
. Deposits that comprise elastotic lesions may be
either eosinophilic (elastosis perforans serpiginosa)—like drusen—or
basophilic (actinic elastosis). Elastotic lesions typically contain
vitronectin (37)
, amyloid P component (63)
,
and complement proteins (64)
, all of which have been
identified as components of drusen in this study. Although drusen
contain a vitronectin and amyloid P component, they do not appear to
contain elastin or elastin-associated fibrillin (32)
,
suggesting that they are not derived from hyperplasia and/or
rearrangement of the elastic fibers in Bruch’s membrane. As such, it
is unlikely that they are related to elastotic deposits.
However, one should not conclude that processes similar to those that
occur in dermal elastosis/degeneration are not responsible for changes
in the elastic lamina of Bruch’s membrane observed with aging and in
patients with AMD (65
, 66)
. Marked changes in the
structure of elastic fibers are observed in aging and in a variety of
disease processes such as atherosclerosis, emphysema, and some
heritable diseases affecting the skin. In pseudoxanthoma elasticum, the
prototypical heritable elastin disease (67
, 68)
, the
integrity of Bruch’s membrane is profoundly affected, leading to the
formation of angioid streaks (69)
. It is conceivable that
at least some forms of AMD could stem from such pathological changes
within Bruch’s membrane that are induced by specific gene mutations or
biological processes also involved in elastosis.
Relationship between drusen and dense deposits
Abnormal basement membrane-associated deposits also appear in
inherited and acquired disorders involving the kidney glomerulus. Dense
deposit disease (a manifestation of membranoproliferative
glomerulonephritis type II) is characterized histologically and
ultrastructurally by the appearance of amorphous, electron dense
deposits that accumulate in kidney basement membranes
(70)
. Extrarenal sites of deposition have also been
observed in patients with dense deposit disease. These include deposits
in the spleen (71)
and in Bruch’s membrane, which
resemble typical (72)
or basal laminar (73)
drusen funduscopically. Patients with dense deposit disease frequently
develop subretinal neovascular membranes (73
, 74)
,
suggesting that the defect(s) responsible for dense deposit disease can
elicit neovascular changes similar to AMD. Kidney dense deposits are
not amyloids, since they fail to stain with Congo red and lack
ß-pleated fibrillar components. Like drusen, dense deposits are
immunoreactive with antibodies against vitronectin, immunoglobulin, and
complement C5 (38)
. However, though dense deposits share
some compositional features with drusen, the former are electron dense,
osmiophilic structures that characteristically contain complement C3
(which is diagnostic of dense deposits; ref 75
),
complement C1q, type VI collagen, and IgM as major components. Collagen
VI and IgM have not been shown to be drusen constituents in a number of
studies (32
, 76)
(although some Ig light chains were
detected in this study) and labeling of drusen with anti-C3 antibodies
is variable. Collectively, these data suggest that dense deposits are
compositionally similar, although not identical, to drusen.
Relationship between drusen and atherosclerotic plaques
Our results, when combined with those from other laboratories,
suggest that drusen share a number of molecular constituents with
atherosclerotic plaques, including lipids (77)
,
vitronectin (35)
, apolipoprotein E (48
, 78)
,
calcium (79)
, and complement components (34)
.
In view of the documented clinical correlation between advanced AMD and
carotid artery atherosclerosis (39)
, it is conceivable
that a similar pathogenic mechanism may be involved. Like drusen,
atherosclerotic plaques form adjacent to an elastic layer, in the
vicinity of vascular endothelial cells and pericytes (80)
.
Like drusen, atherosclerotic plaques are composed of a number of plasma
proteins. However, apolipoprotein B, a major component of
atherosclerotic plaques (81)
, was not consistently
detected in drusen, although antibodies directed against apolipoprotein
B reacted with blood vessels in the retina and choroidal stroma.
Collectively, these results suggest that although drusen share some
major components with atherosclerotic plaques (e.g., vitronectin,
apolipoprotein E, complement, and lipid), some compositional
differences also exist. We propose that future studies aimed at
examining the compositional relationships between specific drusen
phenotypes and specific forms of arterial disease may help to identify
common pathogenic pathways that contribute to drusen and
atherosclerotic plaque formation.
Drusen contain immune- and inflammatory-related proteins
A few studies have indicated a potential role for immune-mediated
processes in the development of AMD. Most significantly, autoantibodies
have been detected in the sera of some AMD patients (82
, 83)
. Data derived from this investigation provide additional
support for the concept that immune- and inflammatory-mediated
processes may be involved in the development and/or regression of
drusen. Drusen contain several acute-phase reactants, coagulation
proteins, immunoglobulin, activated complement, and proteins that are
involved in the induction or activation of the immune response (see
Table 1
). Vitronectin, for example, is capable of inhibiting
complement-mediated cytolysis (33)
. It may also be
significant that macrophages are observed in the choroid adjacent to
drusen (22
, 84)
. These cells have been implicated in the
development of choroidal neovascularization (85
86
87
88)
, but
might also contribute to drusen accretion, directly or indirectly, by
synthesizing and secreting drusen-associated molecules such as
complement C5, apolipoprotein E, Factor X, and prothrombin. In light of
the suggestion that humoral immune processes may be associated with the
etiology of AMD, it is interesting that drusen of all phenotypes
exhibit intense HLA-DR immunoreactivity. Further studies will be
required to determine the source(s) of drusen-associated HLA-DR
and the putative role of immune-mediated processes in drusen biogenesis
and the etiology of AMD.
Drusen origin and biogenesis
These data suggest that the process of protein accumulation in
drusen is selective. For example, drusen do not contain albumin or
haptoglobin, which, like vitronectin, are abundant plasma proteins (see
also ref 32
) that are present within the choroidal stroma
and vascular lumens (89)
. This contention is strengthened
further by the observation that drusen-associated plasma proteins are
not removed after extensive rinsing and that drusen-associated
vitronectin is present in both its heparin binding and multimeric forms
(32)
.
The precise origin(s) of drusen-associated proteins remains to be
resolved. Some drusen constituents (e.g., plasma proteins such as
amyloid P component and prothrombin) may pass out of choroidal vessels
and into the extracellular space adjacent to the RPE, where they might
bind to one or more ligands associated with developing drusen. Other
drusen constituents might be secreted by local retinal, RPE and/or
choroidal cells. Significantly, this study provides compelling data
that the messages for vitronectin (32)
, complement
proteins C3, C5, and C9, Factor X, and apolipoproteins B and E are
expressed locally by retinal, RPE, and/or choroidal cells (Fig. 3
,
Table 2
; see also refs 90
91
92
). Thus, if these messages
are translated and the encoded proteins secreted, local cell types may
play a significant role in drusen biogenesis.
|
SUMMARY |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONSUMMARYREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  M. Economopoulou, J. Hammer, F. Wang, R. Fariss, A. Maminishkis, and S. S. Miller Expression, Localization, and Function of Junctional Adhesion Molecule-C (JAM-C) in Human Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., March 1, 2009; 50(3): 1454 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Goverdhan, S. I. Khakoo, H. Gaston, X. Chen, and A. J. Lotery Age-Related Macular Degeneration Is Associated with the HLA-Cw*0701 Genotype and the Natural Killer Cell Receptor AA Haplotype Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 5077 - 5082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Ferrara, J. E. Merriam, K. B. Freund, R. F. Spaide, B. S. Takahashi, I. Zhitomirsky, H. F. Fine, L. A. Yannuzzi, and R. Allikmets Analysis of Major Alleles Associated With Age-Related Macular Degeneration in Patients With Multifocal Choroiditis: Strong Association With Complement Factor H Arch Ophthalmol, November 1, 2008; 126(11): 1562 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. V. Jurkunas, I. Rawe, M. S. Bitar, C. Zhu, D. L. Harris, K. Colby, and N. C. Joyce Decreased Expression of Peroxiredoxins in Fuchs' Endothelial Dystrophy Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2956 - 2963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, K. Ohno-Matsui, T. Yoshida, A. Kojima, N. Shimada, K.-i. Nakahama, O. Safranova, N. Iwata, T. C. Saido, M. Mochizuki, et al. Altered Function of Factor I Caused by Amyloid {beta}: Implication for Pathogenesis of Age-Related Macular Degeneration from Drusen J. Immunol., July 1, 2008; 181(1): 712 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thill, N. V. Strunnikova, M. J. Berna, N. Gordiyenko, K. Schmid, S. W. Cousins, D. J. S. Thompson, and K. G. Csaky Late Outgrowth Endothelial Progenitor Cells in Patients with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2696 - 2708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Klein, M. D. Knudtson, and B. E. K. Klein Pulmonary Disease and Age-Related Macular Degeneration: The Beaver Dam Eye Study Arch Ophthalmol, June 1, 2008; 126(6): 840 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. N. Baird, L. D. Robman, A. J. Richardson, P. N. Dimitrov, G. Tikellis, C. A. McCarty, and R. H. Guymer Gene-environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection Hum. Mol. Genet., May 1, 2008; 17(9): 1299 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ormsby, S. Ranganathan, J. C. Tong, K. M. Griggs, D. P. Dimasi, A. W. Hewitt, K. P. Burdon, J. E. Craig, J. Hoh, and D. L. Gordon Functional and Structural Implications of the Complement Factor H Y402H Polymorphism Associated with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1763 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Edwards, D. Chen, B. L. Fridley, K. M. James, Y. Wu, G. Abecasis, A. Swaroop, M. Othman, K. Branham, S. K. Iyengar, et al. Toll-like Receptor Polymorphisms and Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1652 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rudolf, M. E. Clark, M. F. Chimento, C.-M. Li, N. E. Medeiros, and C. A. Curcio Prevalence and Morphology of Druse Types in the Macula and Periphery of Eyes with Age-Related Maculopathy Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1200 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Gamm, J. N. Melvan, R. L. Shearer, I. Pinilla, G. Sabat, C. N. Svendsen, and L. S. Wright A Novel Serum-Free Method for Culturing Human Prenatal Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 788 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Izumi-Nagai, N. Nagai, K. Ohgami, S. Satofuka, Y. Ozawa, K. Tsubota, K. Umezawa, S. Ohno, Y. Oike, and S. Ishida Macular Pigment Lutein Is Antiinflammatory in Preventing Choroidal Neovascularization Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2555 - 2562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Coffey, C. Gias, C. J. McDermott, P. Lundh, M. C. Pickering, C. Sethi, A. Bird, F. W. Fitzke, A. Maass, L. L. Chen, et al. Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction PNAS, October 16, 2007; 104(42): 16651 - 16656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Robman, O. S. Mahdi, J. J. Wang, G. Burlutsky, P. Mitchell, G. Byrne, R. Guymer, and H. Taylor Exposure to Chlamydia pneumoniae Infection and Age-Related Macular Degeneration: The Blue Mountains Eye Study Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4007 - 4011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R.W. Yates, T. Sepp, B. K. Matharu, J. C. Khan, D. A. Thurlby, H. Shahid, D. G. Clayton, C. Hayward, J. Morgan, A. F. Wright, et al. Complement C3 Variant and the Risk of Age-Related Macular Degeneration N. Engl. J. Med., August 9, 2007; 357(6): 553 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Mullins, M. H. Kuehn, E. A. Faidley, N. A. Syed, and E. M. Stone Differential Macular and Peripheral Expression of Bestrophin in Human Eyes and Its Implication for Best Disease Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3372 - 3380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Herbert, J. A. Deakin, C. Q. Schmidt, B. S. Blaum, C. Egan, V. P. Ferreira, M. K. Pangburn, M. Lyon, D. Uhrin, and P. N. Barlow Structure Shows That a Glycosaminoglycan and Protein Recognition Site in Factor H Is Perturbed by Age-related Macular Degeneration-linked Single Nucleotide Polymorphism J. Biol. Chem., June 29, 2007; 282(26): 18960 - 18968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. C. Wu, A. G. Tan, E. Rochtchina, E. J. Favaloro, A. Williams, P. Mitchell, and J. J. Wang Circulating Inflammatory Markers and Hemostatic Factors in Age-Related Maculopathy: A Population-Based Case-Control Study Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 1983 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kamei, K. Yoneda, N. Kume, M. Suzuki, H. Itabe, K.-i. Matsuda, T. Shimaoka, M. Minami, S. Yonehara, T. Kita, et al. Scavenger Receptors for Oxidized Lipoprotein in Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1801 - 1807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sivaprasad, T. Adewoyin, T. A. Bailey, S. S. Dandekar, S. Jenkins, A. R. Webster, and N. V. Chong Estimation of Systemic Complement C3 Activity in Age-Related Macular Degeneration Arch Ophthalmol, April 1, 2007; 125(4): 515 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Laine, H. Jarva, S. Seitsonen, K. Haapasalo, M. J. Lehtinen, N. Lindeman, D. H. Anderson, P. T. Johnson, I. Jarvela, T. S. Jokiranta, et al. Y402H Polymorphism of Complement Factor H Affects Binding Affinity to C-Reactive Protein J. Immunol., March 15, 2007; 178(6): 3831 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang, S. L Connor, E. J Johnson, M. L Klein, S. Hughes, and W. E Connor Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration Am. J. Clinical Nutrition, March 1, 2007; 85(3): 762 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Schaumberg, W. G. Christen, J. E. Buring, R. J. Glynn, N. Rifai, and P. M. Ridker High-Sensitivity C-Reactive Protein, Other Markers of Inflammation, and the Incidence of Macular Degeneration in Women Arch Ophthalmol, March 1, 2007; 125(3): 300 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mecklenburg and U. Schraermeyer An Overview on the Toxic Morphological Changes in the Retinal Pigment Epithelium after Systemic Compound Administration Toxicol Pathol, February 1, 2007; 35(2): 252 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Bora, S. Kaliappan, P. Jha, Q. Xu, B. Sivasankar, C. L. Harris, B. P. Morgan, and P. S. Bora CD59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-Type Age-Related Macular Degeneration J. Immunol., February 1, 2007; 178(3): 1783 - 1790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Johnson, K. E. Betts, M. J. Radeke, G. S. Hageman, D. H. Anderson, and L. V. Johnson Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid PNAS, November 14, 2006; 103(46): 17456 - 17461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hye, S. Lynham, M. Thambisetty, M. Causevic, J. Campbell, H. L. Byers, C. Hooper, F. Rijsdijk, S. J. Tabrizi, S. Banner, et al. Proteome-based plasma biomarkers for Alzheimer's disease. Brain, November 1, 2006; 129(Pt 11): 3042 - 3050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Thakkinstian, S. Bowe, M. McEvoy, W. Smith, and J. Attia Association between Apolipoprotein E Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis Am. J. Epidemiol., November 1, 2006; 164(9): 813 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Thakkinstian, P. Han, M. McEvoy, W. Smith, J. Hoh, K. Magnusson, K. Zhang, and J. Attia Systematic review and meta-analysis of the association between complementary factor H Y402H polymorphisms and age-related macular degeneration Hum. Mol. Genet., September 15, 2006; 15(18): 2784 - 2790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Mandal and R. Ayyagari Complement factor h: spatial and temporal expression and localization in the eye. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4091 - 4097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Clark, V. A. Higman, B. Mulloy, S. J. Perkins, S. M. Lea, R. B. Sim, and A. J. Day His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form J. Biol. Chem., August 25, 2006; 281(34): 24713 - 24720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-I. Lau, S.-J. Chen, C.-Y. Cheng, M.-Y. Yen, F.-L. Lee, M.-W. Lin, W.-M. Hsu, and Y.-H. Wei Association of the Y402H Polymorphism in Complement Factor H Gene and Neovascular Age-Related Macular Degeneration in Chinese Patients. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3242 - 3246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Bora, S. Kaliappan, P. Jha, Q. Xu, J.-H. Sohn, D. B. Dhaulakhandi, H. J. Kaplan, and P. S. Bora Complement Activation via Alternative Pathway Is Critical in the Development of Laser-Induced Choroidal Neovascularization: Role of Factor B and Factor H J. Immunol., August 1, 2006; 177(3): 1872 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Dashti, G McGwin, C Owsley, and C A Curcio Plasma apolipoproteins and risk for age related maculopathy Br. J. Ophthalmol., August 1, 2006; 90(8): 1028 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Li, M. E. Clark, M. F. Chimento, and C. A. Curcio Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3119 - 3128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Schaumberg, W. G. Christen, P. Kozlowski, D. T. Miller, P. M. Ridker, and R. Y. L. Zee A Prospective Assessment of the Y402H Variant in Complement Factor H, Genetic Variants in C-Reactive Protein, and Risk of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2336 - 2340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wiggs Complement factor h and macular degeneration: the genome yields an important clue. Arch Ophthalmol, April 1, 2006; 124(4): 577 - 578. [Full Text] [PDF]
|
|
|
|
|
|
M. Nozaki, B. J. Raisler, E. Sakurai, J. V. Sarma, S. R. Barnum, J. D. Lambris, Y. Chen, K. Zhang, B. K. Ambati, J. Z. Baffi, et al. Drusen complement components C3a and C5a promote choroidal neovascularization PNAS, February 14, 2006; 103(7): 2328 - 2333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sepp, J. C. Khan, D. A. Thurlby, H. Shahid, D. G. Clayton, A. T. Moore, A. C. Bird, J. R. W. Yates, and the Genetic Factors in AMD Study Group Complement Factor H Variant Y402H Is a Major Risk Determinant for Geographic Atrophy and Choroidal Neovascularization in Smokers and Nonsmokers Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 536 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Thurman and V. M. Holers The Central Role of the Alternative Complement Pathway in Human Disease J. Immunol., February 1, 2006; 176(3): 1305 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Johnson, M. N. Brown, B. C. Pulliam, D. H. Anderson, and L. V. Johnson Synaptic Pathology, Altered Gene Expression, and Degeneration in Photoreceptors Impacted by Drusen Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4788 - 4795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dasch, A. Fuhs, T. Behrens, A. Meister, J. Wellmann, M. Fobker, D. Pauleikhoff, and H.-W. Hense Inflammatory Markers in Age-Related Maculopathy: Cross-sectional Analysis From the Muenster Aging and Retina Study Arch Ophthalmol, November 1, 2005; 123(11): 1501 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Mullins, K. T. Oh, E. Heffron, G. S. Hageman, and E. M. Stone Late Development of Vitelliform Lesions and Flecks in a Patient With Best Disease: Clinicopathologic Correlation Arch Ophthalmol, November 1, 2005; 123(11): 1588 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. Conley, A. Thalamuthu, J. Jakobsdottir, D. E. Weeks, T. Mah, R. E. Ferrell, and M. B. Gorin Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy Hum. Mol. Genet., July 15, 2005; 14(14): 1991 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Strauss The Retinal Pigment Epithelium in Visual Function Physiol Rev, July 1, 2005; 85(3): 845 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Seddon, S. George, B. Rosner, and N. Rifai Progression of Age-Related Macular Degeneration: Prospective Assessment of C-Reactive Protein, Interleukin 6, and Other Cardiovascular Biomarkers Arch Ophthalmol, June 1, 2005; 123(6): 774 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bok Evidence for an inflammatory process in age-related macular degeneration gains new support PNAS, May 17, 2005; 102(20): 7053 - 7054. [Full Text] [PDF]
|
|
|
|
|
|
G. S. Hageman, D. H. Anderson, L. V. Johnson, L. S. Hancox, A. J. Taiber, L. I. Hardisty, J. L. Hageman, H. A. Stockman, J. D. Borchardt, K. M. Gehrs, et al. From The Cover: A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration PNAS, May 17, 2005; 102(20): 7227 - 7232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Goverdhan, M. W. Howell, R. F. Mullins, C. Osmond, P. R. Hodgkins, J. Self, K. Avery, and A. J. Lotery Association of HLA Class I and Class II Polymorphisms with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., May 1, 2005; 46(5): 1726 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Haines, M. A. Hauser, S. Schmidt, W. K. Scott, L. M. Olson, P. Gallins, K. L. Spencer, S. Y. Kwan, M. Noureddine, J. R. Gilbert, et al. Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration Science, April 15, 2005; 308(5720): 419 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Edwards, R. Ritter III, K. J. Abel, A. Manning, C. Panhuysen, and L. A. Farrer Complement Factor H Polymorphism and Age-Related Macular Degeneration Science, April 15, 2005; 308(5720): 421 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Klein, C. Zeiss, E. Y. Chew, J.-Y. Tsai, R. S. Sackler, C. Haynes, A. K. Henning, J. P. SanGiovanni, S. M. Mane, S. T. Mayne, et al. Complement Factor H Polymorphism in Age-Related Macular Degeneration Science, April 15, 2005; 308(5720): 385 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Li, J. B. Presley, X. Zhang, N. Dashti, B. H. Chung, N. E. Medeiros, C. Guidry, and C. A. Curcio Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy J. Lipid Res., April 1, 2005; 46(4): 628 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Bora, J.-H. Sohn, J. M. C. Cruz, P. Jha, H. Nishihori, Y. Wang, S. Kaliappan, H. J. Kaplan, and N. S. Bora Role of Complement and Complement Membrane Attack Complex in Laser-Induced Choroidal Neovascularization J. Immunol., January 1, 2005; 174(1): 491 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N.H. V. Chong, J. Keonin, P. J. Luthert, C. I. Frennesson, D. M. Weingeist, R. L. Wolf, R. F. Mullins, and G. S. Hageman Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch's Membrane Correspond to the Distribution of Lesions Associated with Age-Related Macular Degeneration Am. J. Pathol., January 1, 2005; 166(1): 241 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Zarbin Current Concepts in the Pathogenesis of Age-Related Macular Degeneration Arch Ophthalmol, April 1, 2004; 122(4): 598 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Schultz, M. L. Klein, A. J. Humpert, C. W. Luzier, V. Persun, M. Schain, A. Mahan, C. Runckel, M. Cassera, V. Vittal, et al. Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family Hum. Mol. Genet., December 15, 2003; 12(24): 3315 - 3323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Ikram, R. van Leeuwen, J. R. Vingerling, A. Hofman, and P. T. V. M. de Jong Relationship between Refraction and Prevalent as well as Incident Age-Related Maculopathy: The Rotterdam Study Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 3778 - 3782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Rakic, V. Lambert, M. Deprez, J.-M. Foidart, A. Noel, and C. Munaut Estrogens Reduce the Expression of YKL-40 in the Retina: Implications for Eye and Joint Diseases Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1740 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Yoshida, A Yoshida, T Ishibashi, Y Kumano, and T Matsui Presence of vitronectin in neovascularised cornea of patient with gelatinous drop-like dystrophy Br. J. Ophthalmol., March 1, 2003; 87(3): 368 - 369. [Full Text] [PDF]
|
|
|
|
|
|
J. W. Crabb, M. Miyagi, X. Gu, K. Shadrach, K. A. West, H. Sakaguchi, M. Kamei, A. Hasan, L. Yan, M. E. Rayborn, et al. From the Cover: Drusen proteome analysis: An approach to the etiology of age-related macular degeneration PNAS, November 12, 2002; 99(23): 14682 - 14687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Johnson, W. P. Leitner, A. J. Rivest, M. K. Staples, M. J. Radeke, and D. H. Anderson The Alzheimer's Abeta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration PNAS, September 3, 2002; 99(18): 11830 - 11835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Shahidi, N P Blair, M Mori, J Gieser, and J S Pulido Retinal topography and thickness mapping in atrophic age related macular degeneration Br. J. Ophthalmol., June 1, 2002; 86(6): 623 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. B. Gerl, J. Bohl, S. Pitz, B. Stoffelns, N. Pfeiffer, and S. Bhakdi Extensive Deposits of Complement C3d and C5b-9 in the Choriocapillaris of Eyes of Patients with Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., April 1, 2002; 43(4): 1104 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dithmar, N. A. Sharara, C. A. Curcio, N.-A. Le, Y. Zhang, S. Brown, and H. E. Grossniklaus Murine High-Fat Diet and Laser Photochemical Model of Basal Deposits in Bruch Membrane Arch Ophthalmol, November 1, 2001; 119(11): 1643 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Stone, V. C. Sheffield, and G. S. Hageman Molecular genetics of age-related macular degeneration Hum. Mol. Genet., October 1, 2001; 10(20): 2285 - 2292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Munaut, V. Lambert, A. Noel, F. Frankenne, M. Deprez, J.-M. Foidart, and J.-M. Rakic Presence of oestrogen receptor type {beta} in human retina Br. J. Ophthalmol., July 1, 2001; 85(7): 877 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W STITT Advanced glycation: an important pathological event in diabetic and age related ocular disease Br. J. Ophthalmol., June 1, 2001; 85(6): 746 - 753. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Curcio, C. L. Millican, T. Bailey, and H. S. Kruth Accumulation of Cholesterol with Age in Human Bruch's Membrane Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 265 - 274. [Abstract] [Full Text]
|
|
|
|
|
|
M. Kliffen, E. Lutgens, M. J A P Daemen, E. D de Muinck, C. M Mooy, and P. T V M de Jong The APO*E3-Leiden mouse as an animal model for basal laminar deposit Br. J. Ophthalmol., December 1, 2000; 84(12): 1415 - 1419. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
