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Published on: April 14, 2023
Scavenger receptors for oxidized lipoprotein in age-related macular degeneration
Motohiro Kamei1, Kazuhito Yoneda, Noriaki Kume
1Department of Ophthalmology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. mkamei@ophthal.med.osaka-u.ac.jp
Purpose:
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.
Insights
Macrophages accumulate in age-related macular degeneration (AMD) lesions to engulf oxidized lipoproteins. This finding suggests targeting oxidative stress and macrophage responses may offer new AMD treatments.
Area of Science:
- Ophthalmology
- Immunology
- Pathogenesis of Age-Related Macular Degeneration (AMD)
Background:
- Macrophage accumulation is implicated in AMD pathogenesis.
- The precise reasons for macrophage accumulation in AMD lesions remain unclear.
- Similarities between AMD and atherosclerosis suggest a potential role for oxidized lipoproteins.
Purpose of the Study:
- To investigate the hypothesis that macrophages accumulate in AMD lesions to uptake oxidized lipoproteins.
- To explore the expression of scavenger receptors for oxidized lipoproteins on macrophages and retinal pigment epithelium (RPE) in AMD.
Main Methods:
- Immunohistochemistry on choroidal neovascular (CNV) membranes from AMD patients.
- Utilized antibodies against oxidized lipoprotein, scavenger receptors (SR-PSOX, LOX-1), RPE (cytokeratin), macrophages (CD68), and vascular cells (von Willebrand factor).
- RT-PCR to detect scavenger receptor mRNAs in CNV membranes.
Main Results:
- Oxidized lipoproteins were detected within CNV membranes.
- SR-PSOX immunostaining was intense, while LOX-1 staining was weak on CNV membranes.
- Macrophages and RPE cells within CNV membranes expressed scavenger receptors for oxidized lipoproteins; both SR-PSOX and LOX-1 mRNAs were detected.
Conclusions:
- Oxidized lipoproteins are present in AMD lesions.
- Macrophages and RPE cells in AMD express scavenger receptors, indicating a mechanism for oxidized lipoprotein uptake.
- Macrophage accumulation in AMD may be driven by oxidized lipoprotein uptake, suggesting therapeutic strategies targeting oxidative stress and macrophage responses.
