Anatomical and Gene Expression Changes in the Retinal Pigmented Epithelium Atrophy 1 (rpea1) Mouse: A Potential Model of Serous Retinal Detachment

Abstract

PurposeThe purpose of this study was to examine the rpea1 mouse whose retina spontaneously detaches from the underlying RPE as a potential model for studying the cellular effects of serous retinal detachment (SRD).MethodsOptical coherence tomography (OCT) was performed immediately prior to euthanasia; retinal tissue was subsequently prepared for Western blotting, microarray analysis, immunocytochemistry, and light and electron microscopy (LM, EM).ResultsBy postnatal day (P) 30, OCT, LM, and EM revealed the presence of small shallow detachments that increased in number and size over time. By P60 in regions of detachment, there was a dramatic loss of PNA binding around cones in the interphotoreceptor matrix and a concomitant increase in labeling of the outer nuclear layer and rod synaptic terminals. Retinal pigment epithelium wholemounts revealed a patchy loss in immunolabeling for both ezrin and aquaporin 1. Anti-ezrin labeling was lost from small regions of the RPE apical surface underlying detachments at P30. Labeling for tight-junction proteins provided a regular array of profiles outlining the periphery of RPE cells in wild-type tissue, however, this pattern was disrupted in the mutant as early as P30. Microarray analysis revealed a broad range of changes in genes involved in metabolism, signaling, cell polarity, and tight-junction organization.ConclusionsThese data indicate changes in this mutant mouse that may provide clues to the underlying mechanisms of SRD in humans. Importantly, these changes include the production of multiple spontaneous detachments without the presence of a retinal tear or significant degeneration of outer segments, changes in the expression of proteins involved in adhesion and fluid transport, and a disrupted organization of RPE tight junctions that may contribute to the formation of focal detachments.

The exocyst is required for photoreceptor ciliogenesis and retinal development

“…known survival effect of rods on cones (33) (e.g. PNA lectin localization from collapsed cone outer segments to the OPL and IPL has been observed in retina degeneration models (44)). Given the histologic severity of the phenotype, it is not surprising that, by ERG testing, the Exoc5 photoreceptor-specific knock-out mice were completely blind by 6 weeks of age.…”

A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction

“…Given that SLC4A5 transport functions have been documented in epithelial tissues [18][19][20][21][22][23] and that retinal detachment in mice is associated with RPE dysfunction [31][32][33], we considered the hypothesis that a loss of SLC4A5 function in the RPE might contribute to the reported retinal detachment and accompanying ocular phenotypes in Slc4a5 mutant mice. Our studies support this hypothesis and advance our understanding of SLC4A5 function at the outer BRB.…”