Identification of a natively resilient but poorly regenerating retinal ganglion cell type in the G protein-coupled receptor 88-Cre transgenic mouse

Abstract

Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss. In mice, there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration. Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88. Motivated to study this retinal ganglion cell type, we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential. Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells. Interestingly, we find that ON-direction-selective retinal ganglion cells are resilient, but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments. Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.