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Nicolas Cuenca, Laura Fernandez-Sanchez, Antonia Angulo, Isabel Pinilla, Jose Martin-Nieto, Pedro Lax; Müller And Astrocyte Cell Changes With Aging In The P23H Rat Retina And TUDCA Neuroprotective Effects. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5467.
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© ARVO (1962-2015); The Authors (2016-present)
In retinitis pigmentosa, secondarily to the loss of photoreceptors a reduction of retinal vascularization and gliosis take place. TUDCA is capable of preventing the loss of rod photoreceptors and the electroretinographic response in different animal models of this disease. The purpose of this study was to investigate changes in glial cells taking place with aging in the retina of P23H rats and the preventive effect of the antiapoptotic agent, TUDCA.
Homozygous P23H line-3 rats aged from P18 to 16 months were used to study the evolution of the disease, and SD rats were used as controls. To evaluate the effect of the antiapoptotic drug on this degeneration P23H rats were injected with TUDCA (500 mg/kg, i.p.) weekly from 20 days to 4 months old. Whole-mount retinas were subjected to lectin staining to reveal the retinal vascular plexus, and antibodies to GFAP and connexin43 were used to observe the relationship of astrocytes with vessels. Immunolabeling with antibodies against GFAP and transducin was used to visualize Müller cells and cone photoreceptors.
In old SD rats Müller cells express GFAP in the peripheral retina, whereas in the P23H rat GFAP expression starts at around 2 months. At 4 months, P23H Müller cells display an unusual distribution with fireworks-like appearance in the outermost photoreceptor layer, which disappears at 16 months of age. Inside these structures cone cell bodies distribute along the radial processes of Müller cells and their outer segments locate around the "fireworks" edges forming circles. TUDCA treatment of rats until 4 months old prevents in part the formation of these structures. It has been reported that astrocyte cells are able to reenter the cell cycle in under pathological conditions to maintain homeostasis. In aged SD rats an increase of the astrocyte cell number was found. At 4 months the number of astrocytes also increased in the P23H rat retina compared with SD, being even higher in TUDCA-treated animals. Astrocytes exhibited a deteriorated morphology, whereas in TUDCA-treated animals astrocytes kept a similar morphology than in control rats.
Glial cells undergo important changes in their number and morphology with aging and in retinitis pigmentosa. TUDCA can prevent astrocyte and Müller cell changes in the P23H rat retina at 4 months of age. This work suggests that TUDCA could be useful for preventive treatment of retinitis pigmentosa.
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