The role of macrophage class a scavenger receptors in a laser-induced murine choroidal neovascularization model.
OBJECTIVE
Laser-induced choroidal neovascularization (CNV) is a widely used model to mimic many features of CNV resulting from wet AMD. Macrophages have been implicated in the pathogenesis of AMD. Class A scavenger receptors, scavenger receptor-A (SR-A) and macrophage receptor with collagenous domain (MARCO), are expressed on macrophages and are associated with macrophage function. The goal of this study is to examine the role of macrophage scavenger receptors in immune cell recruitment and the formation of CNV.


METHODS
Laser photocoagulation was performed in wild-type and knockout mice with deletion of SR-A (SR-A(-/-)), MARCO (MARCO(-/-)), or both SR-A and MARCO double knockout (DKO). Immune cell recruitment at different time points and CNV lesions at 14 days after laser treatment were evaluated through immunostaining and confocal microscopy. Microarray analysis was performed in eyes 1 day after laser injury.


RESULTS
Wild-type eyes showed higher chemokine/receptor expression compared with knockout eyes after laser injury. Scavenger receptor deficiency markedly impaired the recruitment of neutrophils and macrophages to CNV lesions at 1- and 3-days post laser injury, respectively. Significantly reduced CNV volumes were found in the eyes from scavenger receptor knockout mice compared with wild-type mice.


CONCLUSIONS
The deficiency of scavenger receptors impairs the formation of CNV and immune cell recruitment. Our findings suggest a potential role for scavenger receptors in contributing to CNV formation and inflammation in AMD.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Shayma
S
Jawad
Baoying
B
Liu
Zhiyu
Z
Li
Robert
R
Katamay
Mercedes
M
Campos
Lai
L
Wei
H Nida
HN
Sen
Diamond
D
Ling
Fernando
F
Martinez Estrada
Juan
J
Amaral
Chi-Chao
CC
Chan
Robert
R
Fariss
Siamon
S
Gordon
Robert B
RB
Nussenblatt
D000818:Animals; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007150:Immunohistochemistry; D007834:Lasers / Q000009:adverse effects; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D051116:Receptors, Scavenger / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000502:physiology*
D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A
AMD; CNV; macrophages; scavenger receptors