Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration

Summary The group of retinal degenerations, retinitis pigmentosa (RP), comprise more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, RPE and Muller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4 to 10, during rod and cone loss in P23H mice (a RP model) with retinal degeneration, preserved photoreceptor function and normalized Muller glial cell morphology. Single-cell transcriptomics of retinal cells, showed that FGF21 receptor Fgfr1 was specifically expressed in Muller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Muller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.