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Claire Hippert, Amanda C. Barber, Jane C. Sowden, Robin R. Ali, Rachael A. Pearson; Characterisation Of Gliosis In Different Models Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1836.
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Gliosis is a fundamental CNS response to trauma or disease. In the degenerating murine retina, Müller glia increase production of the intermediate filaments GFAP and vimentin and undergo hypertrophy. A proper understanding of the Müller gliotic response in retinal degeneration is essential for therapeutic strategies. Glial scarring is likely to have a major impact on regenerative strategies such as cell transplantation. For example, the glial scar may present a physical barrier or act as a reservoir of inhibitory extracellular matrix (ECM) molecules e.g. chondroitin sulphate proteoglycans (CSPGs). We sought to characterise and compare glial scarring and ECM deposition in different models of retinitis pigmentosa.
Glial scarring was assessed in the neural retinae of rho-/-, Prph2rds/rds, Rds-307+/- and Gnat1-/- mice at early, mid and end stage degeneration using expression of GFAP, vimentin and CSPGs. Expression was assessed by immunohistochemistry and/or western blot. Outer Nuclear Layer (ONL) thickness/density was measured as a marker of disease progression.
Very different levels of GFAP/vimentin expression were observed between the models. The highest in rho-/-, a rapidly degenerating model, and the lowest in the slowly degenerating Gnat1-/-. Prph2rd2/rd2 and Rds-307+/-, which undergo moderate rates of degeneration, have many GFAP+ve processes extending into the ONL, although expression remained relatively constant over time. Prph2rd2/rd2, rds-307+/- and rho-/- mice present a proliferation of GFAP+ve processes at the outer edge of the ONL, extending laterally along the OLM, typical of gliotic scar associated hypertrophy. CSPG deposition increased with time in the rho-/-, becoming very dense in end stage disease, but was virtually absent in the Gnat1-/-. In Prph2rds/rds and Rds-307+/- retinae, CSPG deposition became more dispersed with time.
These results demonstrate that a gliotic response is launched in all the models of RP examined. However, the extent of this response differs between models of degeneration, even when at comparable states of ONL loss.
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