Age-Related Retinal Degeneration Resulting from the Deletion of Shp2 Tyrosine Phosphatase in Photoreceptor

Shp2, a critical SH2-domain-containing tyrosine phosphatase, is essential for cellular regulation and implicated in metabolic disruptions, obesity, diabetes, Noonan syndrome, LEOPARD syndrome, and cancers. This study focuses on Shp2 in rod photoreceptor cells, revealing its enrichment, particularly in rods. Deletion of Shp2 in rods leads to age-dependent photoreceptor degeneration. Shp2 targets occludin (OCLN), a tight junction protein, and its deletion reduces OCLN expression in the retina and retinal pigment epithelium (RPE). Isolation of actively translating mRNAs from rods lacking Shp2, followed by RNA sequencing, reveals alterations in cell cycle regulation. Altered retinal metabolism is observed in retinal cells lacking Shp2. Our studies indicate that Shp2 is crucial for maintaining the structure and function of photoreceptors. Total tissue lysate and Rod-TRAP RNASeq data were collected from the retinas of 2-week-old littermate control mice (RiboTag;Shp2fl/+;i75-Rod-Cre) and experimental rod photoreceptor Shp2 knockout mice (RiboTag;Shp2fl/fl;i75-Rod-Cre).