LAMP2 Deficiency Enhances Susceptibility to Oxidative-Stress-Induced RPE Degeneration

Abstract

Purpose : Lysosome-associated membrane protein 2 (LAMP2) is essential for autophagosome maturation. Previous studies demonstrated the formation of basal laminar deposits in aged LAMP2 KO mice. This study investigates whether LAMP2 deficiency increases vulnerability to oxidative stress.

Methods : We induced oxidative stress in the retinas of LAMP2 KO and wild-type (WT) mice via intravenous Sodium Iodate (NaIO3) injections. We assessed changes in RPE morphology and retinal microglia/macrophages, using ZO-1 and Iba-1 immunolabeling, respectively. Analysis was performed with ImageJ 2.0 software, detailing total and degenerated RPE areas, and counting microglia/macrophages in retinal layers.

Results : LAMP2 KO mice showed significant RPE degeneration (34.6±1.8% of total fundus area) following a low NaIO3 dose (10 mg/kg), compared to minimal changes in WT mice (0.1±0.4%) and untreated LAMP2 KO mice (0±0%). Macrophages with an ameboid morphology migrated to the outer nuclear layers and subretinal spaces during RPE degeneration observed in LAMP2 KO mice. The numbers of macrophage counted differed significantly between WT and LAMP2 KO mice (491±103 vs. 2223±90 cells/mm², P < 0.01).

Conclusions : LAMP2 deficiency may compromise antioxidant capability, leading to the RPE degeneration upon oxidative stress.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.