Rbpms is essential for the specification of retinal ganglion cell identity

The RNA-binding protein RBPMS, characterized by multiple splicing variants and widely recognized as a marker for retinal ganglion cells (RGCs), has a role in embryonic retinal development, aging processes, and neurodegenerative conditions that remain incompletely understood. This research seeks to clarify the role of Rbpms in retinal development and to investigate its pathological changes in the context of aging and neurodegenerative diseases. By employing immunolabeling of RBPMS and Brn3a on retinal sections from aging mouse models under oxidative stress and elevated hydrostatic pressure and analyzing ocular tissue from wild-type (WT) and Rbpms knockout embryos, we observed that RBPMS predominantly resides in the cytoplasm of RGCs in the ganglion cells layer. Our findings show decreased RBPMS-positive RGC density and immunoreactivity with age and under stress conditions in mice. The absence of Rbpms disrupted the number of PAX6+ cells and Iba1+ microglia, suggesting a crucial role in RGC specification from retinal progenitor cells (RPC) and coordinating neuronal survival and regeneration. This resulted in a significant reduction in the density of Brn3a-positive RGCs and the SMI-32 area fraction. However, no significant difference in the NBL layer cell numbers or TUJ1+ primary neurons between Rbpms -/- and WT retinas was observed, indicating that Rbpms deficiency delays retinal layering without altering overall ocular morphology. This study highlights the essential function of RBPMS in the expression decline during aging and neurodegeneration, underscoring its significant role in guiding RPC differentiation towards specific neural lineages.