FGF2 Deficiency Modulates Early Microglial Responses Without Affecting Photoreceptor Survival in a Retinitis
Felia C Haffelder1, Nundehui Díaz-Lezama1, Zeynep Okutan1
1Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
Abstract:
Fibroblast growth factor 2 (FGF2) is expressed in retinal Müller glia cells, and its expression increases in response to photoreceptor degeneration. To investigate the physiological relevance of FGF2, we analyzed retinal morphology and cellular responses in Fgf2-deficient (Fgf2-/-) mice. Loss of FGF2 did not affect photoreceptor survival, retinal vasculature, or retinal pigment epithelium (RPE) integrity. To further understand its role in retinal degeneration, Fgf2-/- mice were crossed with Pde6bSTOP/STOP mice, a model of retinitis pigmentosa (RP). We then analyzed outer nuclear layer thickness, cone number, rod outer segments length, RPE morphology, and microglia number in Fgf2-/-Pde6bSTOP/STOP and Pde6bSTOP/STOP mice. Although FGF2 was upregulated in degenerating photoreceptor cells in the Pde6bSTOP/STOP retina, its absence did not accelerate photoreceptor loss in Fgf2-/-Pde6bSTOP/STOP mice. Interestingly, microglia numbers were significantly changed at early disease stages in Fgf2-/-Pde6bSTOP/STOP retinas compared with Pde6bSTOP/STOP controls, suggesting that FGF2 modulates inflammatory signaling. Together, these results show that loss of FGF2 does not alter photoreceptor degeneration kinetics or retinal morphology, but may contribute to the regulation of early microglial accumulation during degeneration.
Insights
Fibroblast growth factor 2 (FGF2) loss did not impact photoreceptor degeneration in mice. However, FGF2 absence altered early microglial cell accumulation during retinal degeneration, suggesting a role in inflammatory signaling.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Fibroblast growth factor 2 (FGF2) is present in retinal Müller glia and elevates during photoreceptor degeneration.
- The precise physiological role of FGF2 in retinal degeneration remains unclear.
Purpose of the Study:
- To investigate the physiological relevance of FGF2 in retinal degeneration.
- To analyze the impact of FGF2 deficiency on retinal morphology and cellular responses.
Main Methods:
- Retinal morphology and cellular responses were analyzed in FGF2-deficient (Fgf2-/-) mice.
- Fgf2-/- mice were crossed with Pde6bSTOP/STOP mice, a model for retinitis pigmentosa (RP), to assess FGF2's role in a disease context.
- Key parameters analyzed included outer nuclear layer thickness, cone number, rod outer segment length, RPE morphology, and microglia number.
Main Results:
- FGF2 deficiency did not affect photoreceptor survival, retinal vasculature, or RPE integrity in baseline conditions.
- In the RP model, FGF2 absence did not accelerate photoreceptor loss despite FGF2 upregulation in degenerating cells.
- A significant alteration in microglia numbers was observed at early disease stages in Fgf2-/- RP mice compared to controls, indicating FGF2's modulation of inflammatory signaling.
Conclusions:
- Loss of FGF2 does not alter the kinetics of photoreceptor degeneration or overall retinal morphology.
- FGF2 may play a role in regulating the early accumulation of microglia during retinal degeneration, potentially influencing inflammatory responses.
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