Soluble guanylate cyclase deficiency drives retinal ganglion cell neurodegeneration with age in female mice through disrupted oxidative metabolism.

ABSTRACT: Dysfunctional cGMP signaling is implicated in multiple neurodegenerative diseases of the central nervous system (CNS), including glaucoma, an optic neuropathy and leading cause of irreversible blindness. Female mice lacking the alpha catalytic subunit of soluble guanylate cyclase (sGCα1^-/-), the active site that binds nitric oxide (NO) to produce cGMP, exhibit progressive retinal ganglion cell (RGC) degeneration with age. Yet, the role of sGC in age- and sex-dependent RGC function remains uncharacterized. We investigated how preventing NO binding to sGC influences RGC function in the context of aging and sex by combining bulk and single-cell RNA sequencing, Western blotting, mitochondrial ultrastructural analysis, visual acuity measurements, and in vivo measurements of retinal o

SUBMITTER: Bossardet OL 

PROVIDER: S-EPMC12859072 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature