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Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration
Agustina Noailles1, Victoria Maneu2, Laura Campello1
1Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Abstract:
Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II(+) cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat's life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies.
Insights
In dominant retinitis pigmentosa models, microglia activation and inflammation persist lifelong, even after photoreceptor loss. Targeting this persistent neuroinflammation with anti-inflammatory drugs may improve retinal health for cell therapies.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Microglia are central nervous system immune cells, including in the retina.
- Activated microglia can adopt a harmful phagocytic phenotype, releasing pro-inflammatory cytokines.
- Dominant retinitis pigmentosa involves retinal degeneration.
Purpose of the Study:
- To investigate longitudinal microglial changes during retinal degeneration in the P23H rat model of dominant retinitis pigmentosa.
- To correlate microglial activation with pro-inflammatory cytokine expression and retinal function.
Main Methods:
- Immunohistochemistry and flow cytometry to analyze microglial phenotype, morphology, and density.
- Cytokine antibody array to assess inflammatory markers.
- Electroretinograms to evaluate retinal function.
Main Results:
- Increased inflammatory cells were observed in P23H rat retinas, sclera, choroid, and ciliary body compared to controls.
- Older P23H rats showed more amoeboid MHC-II(+) microglia, correlating with elevated pro-inflammatory cytokines.
- Retinal neuroinflammation persisted throughout the lifespan in the P23H model, despite photoreceptor depletion.
Conclusions:
- Persistent retinal neuroinflammation occurs in the P23H rat model of dominant retinitis pigmentosa.
- Anti-inflammatory therapies in later disease stages could enhance retinal health.
- This approach may improve the efficacy of cellular or gene therapies by preserving remaining retinal cells.
