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.
Highlights
Retinal microglia develop an amoeboid reactive form lacking cellular processes and exhibiting macrophage behavior
To look for possible signs of microglia activation, retinal sections from 1, 4- and 12-month-old SD and P23H rats were immunostained with antibodies against Iba[1], constitutively expressed by microglia[36], and MHC-II, the upregulation of which is a hallmark of reactive microglia[37] (Fig. 2)
These results evidenced that the decay of retinal function in the P23H rat correlated with changes in Iba1+ cell morphology and expression of MHC-II
Summary
Retinal microglia develop an amoeboid reactive form lacking cellular processes and exhibiting macrophage behavior. Our objective was to determine the onset of microglia activation in an animal model of RP and to characterize the inflammatory profile of the retina, choroid and sclera at early, intermediate and advanced stages of the disease, with the purpose of clarifying whether retinal neuroinflammation persists once the majority of photoreceptors have died. We hope this knowledge will help in the design of more effective therapeutic approaches
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