Abstract
Purpose :
The changes in gene expression in the retinal pigment epithelium (RPE) at early stages of degeneration are not well understood. Aldh1a1 gene knockout (KO) mice, exhibiting choroidal hypoplasia from birth, show signs similar to atrophic age-related macular degeneration (AMD) as they age (S Goto, et al., ARVO, 2019). This study aims to morphologically and physiologically analyze middle-aged Aldh1a1 KO mice showing early signs of RPE degeneration and to conduct comprehensive gene expression analysis of isolated RPE to investigate the early pathophysiology of RPE degeneration.
Methods :
Eyes from 10-month-old wild-type (WT) and Aldh1a1 KO mice were enucleated for immunohistochemical analysis of RPE flat mounts using ZO-1, electron microscopy of eye sections, electrophysiological analysis including electroretinography (ERG), optokinetic tracking (OKT), and RNA-sequence analysis of isolated RPE.
Results :
The RPE cell count in flat mounts did not differ between WT and KO mice, with no significant differences observed in ERG and OKT. However, electron microscopy revealed slight disorganization in the basal membrane invagination structures in KO RPE, indicating early signs of degeneration. RNA sequencing showed decreased expression of MFRP and CTRP5, genes implicated in late-onset retinal degeneration, in Aldh1a1 KO RPE.
Conclusions :
Early RPE degeneration characterized by choroidal hypoplasia in middle-aged Aldh1a1 KO mice suggests a potential role in the pathogenesis of atrophic AMD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.