NMNAT2 is downregulated in glaucomatous RGCs, and RGC-specific gene therapy rescues neurodegeneration and visual function.

ABSTRACT: The lack of neuroprotective treatments for retinal ganglion cells (RGCs) and optic nerve (ON) is a central challenge for glaucoma management. Emerging evidence suggests that redox factor NAD⁺ decline is a hallmark of aging and neurodegenerative diseases. Supplementation with NAD⁺ precursors and overexpression of NMNAT1, the key enzyme in the NAD⁺ biosynthetic process, have significant neuroprotective effects. We first profile the translatomes of RGCs in naive mice and mice with silicone oil-induced ocular hypertension (SOHU)/glaucoma by RiboTag mRNA sequencing. Intriguingly, only NMNAT2, but not NMNAT1 or NMNAT3, is significantly decreased in SOHU glaucomatous RGCs, which we confirm by in situ hybridization. We next demonstrate that AAV2 intravitreal inject

SUBMITTER: Fang F 

PROVIDER: S-EPMC9077370 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature