Scavenger receptors for oxidized lipoprotein in age-related macular degeneration.
OBJECTIVE
The accumulation of macrophages is known to be involved in the pathogenesis of age-related macular degeneration (AMD), but the reasons why macrophages accumulate in AMD lesions have not been determined. Because the histopathology of AMD has some factors common with those of atherosclerosis, the authors hypothesized that macrophages accumulate to take up oxidized lipoproteins in the eyes of patients with AMD, as has been demonstrated in atherosclerosis.


METHODS
Immunohistochemistry was performed on 10 surgically excised choroidal neovascular (CNV) membranes from eyes with AMD. An antibody against oxidized lipoprotein and antibodies against the scavenger receptors SR-PSOX and LOX-1 were used. Antibodies against cytokeratin, CD68, and von Willebrand factor were used to identify retinal pigment epithelium (RPE), macrophages, and vascular endothelial cells, respectively. RT-PCR was performed to detect the mRNAs of the scavenger receptors in the CNV membranes.


RESULTS
Oxidized lipoproteins were immunohistochemically detected in the CNV membranes. Intense immunostaining was observed at the surface of the CNV membranes with the SR-PSOX antibody, whereas LOX-1 immunostaining was weak. Cells expressing scavenger receptors were found to be predominantly macrophages with a minority of RPE. Both SR-PSOX and LOX-1 mRNAs were detected in CNV membranes.


CONCLUSIONS
Oxidized lipoproteins are present in AMD lesions. Macrophages and RPE in the CNV membranes express cell surface scavenger receptors for oxidized lipoproteins. These findings suggest that macrophages may accumulate to take up oxidized lipoproteins in AMD and that the control of oxidative stress and macrophage responses may therefore be potential treatments for AMD.
Kamei
Motohiro
M
Department of Ophthalmology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. mkamei@ophthal.med.osaka-u.ac.jp
Yoneda
Kazuhito
K
Kume
Noriaki
N
Suzuki
Mihoko
M
Itabe
Hiroyuki
H
Matsuda
Ken-Ichi
K
Shimaoka
Takeshi
T
Minami
Manabu
M
Yonehara
Shin
S
Kita
Toru
T
Kinoshita
Shigeru
S
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D014841:von Willebrand Factor; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D007633:Keratins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E; D014841:von Willebrand Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C423727:CXCL16 protein, human; C495137:OLR1 protein, human; C099252:oxidized low density lipoprotein