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Updated: Nov 7, 2025
Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration
Zhongjie Fu1,2, Chenxi Qiu3, Gael Cagnone4,5
1Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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.
Insights
Fibroblast growth factor 21 (FGF21) treatment preserved photoreceptor function in a retinitis pigmentosa (RP) mouse model. FGF21 enhanced Müller glia, suggesting a potential general therapy for retinal 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.
