Clinical Characterization of Myopic Retinopathy in LRP2^Best-Cre-KO mice

Abstract

Purpose : High myopia affects 1-3% of the population and can cause sight-threatening retinal complication known as myopic retinopathy. The underlying mechanism of myopic retinopathy remains poorly defined. Mutations in the megalin-encoding gene, LRP2, cause high myopia as seen in patients with Donnai-Barrow syndrome. Megalin is highly expressed by retinal pigment epithelial (RPE) cells. We generated a moue model of myopic retinopathy by specific deletion of LRP2 in RPE cells (LRP2^Best-Cre-KO mice) and further characterized retinal degenerative changes in these mice.

Methods : RPE-specific deletion of megalin was achieved by crossing Best1.Cre (C57BL/6J) mice with Lrp2^Lox/Lox mice and the genotype was confirmed by PCR. Optical coherence tomography (OCT) was used to measure axil length, and retinal function was evaluated by electroretinogram (ERG) and optokinetic reflex.

Results : 55% of LRP2^Best-Cre-KO mice had significantly longer axil length compared to WT controls starting at two weeks of age. Further analysis of ocular compartments showed that the anterior chamber depth was significantly decreased whereas the vitreous chamber depth was significantly increased in LRP2^Best-Cre-KO mice compared to WT controls. The LRP2^Best-Cre-KO mice also had thinner retinal thickness in both the inner retinal and outer retinal layers. ERG revealed significantly reduced a-, b-, c- waves and lower oscillatory potentials (Ops). By the age of eight weeks, all eyes in the LRP2^Best-Cre-KO group developed tessellated retina, 77% of eyes had peripapillary atrophy, and 10% of eyes developed retinoschisis.

Conclusions : The LRP2^Best-Cre-KO mice develop a variety of retinal degenerative changes including tessellation, peripapillary atrophy and retinoschisis. The mouse line is a good model of high-myopia induced retinopathy.

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