biostudies-literatureBossardet OLNEI NIH HHSNational Institutes of HealthNIH HHS4167https://www.ebi.ac.uk/biostudies/studies/S-EPMC12859072biostudies-literatureUnknown16(1)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 oScientific reportsSoluble guanylate cyclase deficiency drives retinal ganglion cell neurodegeneration with age in female mice through disrupted oxidative metabolism.PMC12859072R01 EY0360025R01EY036002Holden JMKonety RGhanem GOBWade SMecca SAlmaoui EKorobkina EDWareham LKSnyder LARex TSBossardet OLClark KLfalseSoluble guanylate cyclase deficiency drives retinal ganglion cell neurodegeneration with age in female mice through disrupted oxidative metabolism.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 o2026-01-01T00:00:00Z2026 Jan2026-06-13T05:28:53.222Z2026-06-13T03:08:51.294ZS-EPMC128590724151369310.1038/s41598-025-34243-5