Role of Mineralocorticoid Receptor in laser-induced choroidal neovascularization

Abstract

Purpose : Neovascular age-related macular degeneration (AMD) accounts for 90% of severe vision loss in AMD patients. The current monthly anti-VEGF treatments are effective in reducing the leakage from choroidal neovascularisation (CNV), but do not induce a total regression of the CNV. Identification of additional therapies is required to reduce patient visits and injections, and to improve outcomes by targeting additional pathways. We aimed to investigate the contribution of mineralocorticoid receptor in laser-induced CNV.

Methods : CNV was induced by Argon laser (532 nm) in eyes of Long-Evans rats. Spironolactone (25mg/kg) was injected subcutaneously daily from day 0 to day 14 after laser. Rats received intravitreal injection of rat anti-VEGF (1.5µg/µl) at day 0 served as positive controls. Fluorescein angiography was performed at day 14 to estimate CNV leakage. The volume of CNV was quantified on choroidal flat mounts. Animals were also killed at day 3 after laser induction; eyes were used for IBA-1 immunolabelling of macrophages/microglia. Expression of MR, pro-inflammatory and pro-angiogenic factors was also assessed using quantitative PCR.

Results : Spironolactone significantly suppressed laser-induced CNV formation by 36% and reduced vascular leakage. MR expression was up-regulated in the neuroretina and retinal pigment epithelium (RPE)-choroidal at day 3. MR antagonist inhibited microglial/macrophage activation and migration towards the CNV lesions, and down-regulated MCP1, IL-1β, TNF-α and iNOS in both neuroretina and RPE-choroid.

Conclusions : Our results suggest that MR activation promotes early inflammation and thus contributes to CNV formation. MR antagonist could be an alternative or complementary treatment of anti-VEGF for CNV.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.