Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• Retinitis pigmentosa (RP) encompasses over 150 genetic defects impacting photoreceptors.
• Identifying common degenerative pathways could enable broad neuroprotective treatments for RP.
• Neuroprotection strategies include supporting cells like retinal pigment epithelial cells and Müller glia.

Purpose of the Study:

• To investigate the neuroprotective potential of fibroblast growth factor 21 (FGF21) in a mouse model of RP.
• To determine the cellular targets and molecular mechanisms of FGF21 in retinal degeneration.

Main Methods:

• Treatment of P23H mice (an RP model) with FGF21 from postnatal week 4-10.
• Assessment of photoreceptor function and Müller glial cell morphology.
• Single-cell transcriptomics analysis of retinal cells to identify FGF21-affected genes and pathways.

Main Results:

• FGF21 treatment preserved photoreceptor function and normalized Müller glial morphology in P23H mice.
• The FGF21 receptor (Fgfr1) was found to be specifically expressed in Müller glia/astrocytes.
• FGF21 primarily influenced genes in Müller glia/astrocytes, upregulating axon development and synapse formation pathways.

Conclusions:

• Enhancing glial axon and synapse formation via FGF21 may preserve retinal function in RP.
• FGF21 shows promise as a general therapeutic approach for various retinal degenerative diseases.