Class A Scavenger Receptors Shed Light on Immune Cell Recruitment and CNV

Scavenger receptors have been identified as cell surface proteins that recognize modified forms of lipoproteins and thereby promote macrophage foam cell formation during atherosclerosis. ¹ We now know that scavenger receptors have a broad role in immune cell biology, including macrophage polarization, innate immune signaling, and cytokine production. ² In this edition of IOVS, Jawad and colleagues ³ asked the question whether knockout of the two class A scavenger receptors, SR-A and MARCO, affects chemokine levels, leukocyte infiltration, and CNV formation in the mouse eye. They used laser-induced damage of Bruch's membrane to trigger CNV formation and thereby modeled the major hallmark of wet AMD. Jawad et al. showed that deficiency of SR-A, MARCO, or both markedly diminished the recruitment of macrophages and neutrophils to early laser lesions, resulting in significantly smaller lesion volumes at late-stage CNV. Using temporal expression profiling with DNA microarrays, the authors also identified a reduced global chemokine and chemokine receptor expression in laser-treated scavenger receptor deficient eyes. This recent study clearly suggests that class A scavenger receptors expressed on macrophages promote a proinflammatory environment and contribute to CNV development in the eye. It will be interesting to see whether class A scavenger receptors interact with the complement system, another important component of AMD-related innate immunity. In the future, scavenger receptors may serve as molecular markers for inflammatory macrophages and targets for immunomodulatory therapies in the eye.