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Ursula Greferath, Emily E. O'Brien, Michael Kalloniatis, Erica L. Fletcher; Characterising Retinal Degeneration In A Novel Mouse Model Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1842. doi: https://doi.org/.
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Retinitis pigmentosa (RP) refers to a family of inherited diseases that lead to blindness. Significant remodelling of inner retinal neurons occurs in mid to late stages of the disease when total loss of photoreceptors has already occurred. We aim to further characterise the cause and progression of events during this phase.
We have used a double mutant transgenic mouse, rd1-FTL. These mice contain a mutation in the β subunit of phosphodiesterase 6 leading to RP and an axon-targeted β-galactosidase (β-gal) reporter system which is under the regulation of the c-fos gene. Neurons that express c-fos also express β-gal in their cell bodies, axons and dendrites allowing complete visualisation of their projections. Retinae from mice between P30 to P365 were either processed as wholemounts or 12µm cryostat sections and immunocytochemically processed. Some tissue was also resin embedded, sectioned at 350nm and processed for post-embedding amino acid immunocytochemistry.
The inner retinal layers were thinner in the rd1-FTL mouse compared with controls indicating a widespread loss of cells. However, remodelling events and glial changes occurred in patches across the retina. An upregulation of β-gal in the central retina was observed in ganglion and amacrine cells adjacent to the optic disc at P120 that spread to cover the entire central retina (>P150) surrounding the optic disc. Labelling was still present following P330. There was a progression of inner retina remodelling events from the central to peripheral retina that matched the spread of β-gal labelling. Notably, Müller cells showed a loss of glutamine synthetase and Kir 4.1 immunoreactivity and an upregulation of cyclin D1 in regions of high β-gal labelling.
We prepose this significant upregulation of β-gal activity may reflect active cellular signalling that indicates inner retinal remodelling. The progression of remodelling events could be linked to the pattern of glial cell dysfunction.
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