Abstract
Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats.Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors.Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas.Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.
Highlights
Retinal macroglia, consisting of astrocytes and Müller cells, play key roles in the homeostasis of retinal neurons, keeping the retina healthy, and functioning properly
To assess the evolution of astrocyte changes during retinal degeneration, the cell density and morphology of retinal astrocytes were studied at different ages in normal and diseased retinas through the immunocytochemical localization of Glial fibrillary acidic protein (GFAP)
In P23H rat retinas, GFAP-positive Müller cell end-feet were observed at the ganglion cell layer (GCL) from P120 to P480 (Figures 1D–F, arrowheads)
Summary
Retinal macroglia, consisting of astrocytes and Müller cells, play key roles in the homeostasis of retinal neurons, keeping the retina healthy, and functioning properly. They are commonly thought to play an important part in the proper development and functioning of the vascular system in the retina, including blood flow and the formation of the blood-retinal barrier (BRB) (Coorey et al, 2012; Kur et al, 2012; Klaassen et al, 2013) Both astrocytes and Müller cells are involved in the survival of retinal cells through the release of neurotrophic factors, providing anti-oxidative support, clearing neurotransmitters and ions from the extraneural space and, as in the brain, supporting the formation and removal of synapses. They are involved in the activation of microglial cells and participate in the regulatory mechanisms of vasodilation and vasoconstriction (Azevedo et al, 2009; Bringmann and Wiedemann, 2012; Coorey et al, 2012; Bringmann et al, 2013; Cuenca et al, 2014; Chong and Martin, 2015; Vecino et al, 2015)
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