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Abstract #106750 Published in IGR 23-3
Secreted phosphoprotein 1 slows neurodegeneration and rescues visual function in mouse models of aging and glaucoma
Li S; Jakobs TCCell reports 2022; 41: 111880
Aging causes an irreversible, cumulative decline in neuronal function. Using the visual system as a model, we show that astrocytes play a critical role in maintaining retinal ganglion cell health and that deletion of SPP1 (secreted phosphoprotein 1, or osteopontin) from astrocytes leads to increased vulnerability of ganglion cells to age, elevated intraocular pressure, and traumatic optic nerve damage. Overexpression of SPP1 slows the age-related decline in ganglion cell numbers and is highly protective of visual function in a mouse model of glaucoma. SPP1 acts by promoting phagocytosis and secretion of neurotrophic factors while inhibiting production of neurotoxic and pro-inflammatory factors. SPP1 up-regulates transcription of genes related to oxidative phosphorylation, functionally enhances mitochondrial respiration, and promotes the integrity of mitochondrial microstructure. SPP1 increases intracellular ATP concentration via up-regulation of VDAC1.
Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA; Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, MA 02114, USA. Electronic address: song_li@meei.harvard.edu.
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