PT - JOURNAL ARTICLE AU - Li, Song AU - Jakobs, Tatjana C TI - Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage AID - 10.26508/lsa.202301976 DP - 2023 Aug 01 TA - Life Science Alliance PG - e202301976 VI - 6 IP - 8 4099 - https://www.life-science-alliance.org/content/6/8/e202301976.short 4100 - https://www.life-science-alliance.org/content/6/8/e202301976.full SO - Life Sci. Alliance2023 Aug 01; 6 AB - Glaucoma is a common neurodegenerative disorder characterized by retinal ganglion cell death, astrocyte reactivity in the optic nerve, and vision loss. Currently, lowering the intraocular pressure (IOP) is the first-line treatment, but adjuvant neuroprotective approaches would be welcome. Vitamin C possesses neuroprotective activities that are thought to be related to its properties as a co-factor of enzymes and its antioxidant effects. Here, we show that vitamin C promotes a neuroprotective phenotype and increases gene expression related to neurotropic factors, phagocytosis, and mitochondrial ATP production. This effect is dependent on the up-regulation of secreted phosphoprotein 1 (SPP1) in reactive astrocytes via the transcription factor E2F1. SPP1+ astrocytes in turn promote retinal ganglion cell survival in a mouse model of glaucoma. In addition, oral administration of vitamin C lowers the IOP in mice. This study identifies an additional neuroprotective pathway for vitamin C and suggests a potential therapeutic role of vitamin C in neurodegenerative diseases such as glaucoma.