Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration

Zhongjie Fu, Chenxi Qiu, Gael Cagnone, Yohei Tomita, Shuo Huang, Bertan Cakir, Yumi Kotoda, William Allen, Edward Bull, James D. Akula, Jean Sébastien Joyal, Ann Hellström, Saswata Talukdar, Lois E.H. Smith

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The group of retinal degenerations, retinitis pigmentosa (RP), comprises 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, retinal pigment epithelial cells, and Müller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4–10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Müller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Müller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Müller 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.

Original languageEnglish
Article number102376
JournaliScience
Volume24
Issue number4
DOIs
Publication statusPublished - 2021 Apr 23
Externally publishedYes

Keywords

  • Cellular Neuroscience
  • Neuroscience
  • Sensory Neuroscience

ASJC Scopus subject areas

  • General

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