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M.J. Campbell, M. Humphries, A. Kennan, P. Humphries, B. Brankin; Outer Limiting Membrane Integrity and Photoreceptor Cell Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2849.
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Retinitis pigmentosa (RP) comprises a heterogenous group of inherited diseases that are characterised by primary degeneration of rod photoreceptors and secondary degeneration of cone photoreceptors in the retina. RP represents a major cause of progressive retinal disease worldwide. The Outer Limiting Membrane (OLM) of the mammalian retina lies at the apical site of the Outer Nuclear Layer (ONL) of the photoreceptors, and contains specialized adherens junctions, which are present between the photoreceptor cells and the Müller glial cells. The multi–protein complexes, which comprise these adherens junctions, allow for the maintenance of the photoreceptor cell skeleton, shape and its overall health and integrity. The purpose of this work was to examine OLM integrity with regard to adherens junction protein expression in a mouse model of RP.
Using a mouse model of autosomal dominant RP with retinopathy induced by targeted disruption of the rhodopsin gene (Rho–/–), we have examined expression patterns of a series of adherens junction associated proteins at the OLM of the Rho(–/–) mouse.
We have found discontinuous and fragmented expression of the adherens junction associated proteins Zonula Occludens–1 (ZO–1), Beta–Catenin and p120–Catenin at the OLM of the Rho(–/–) mice compared to WT mice of the same age and genetic background. While we show aberrant expression of ZO–1, Beta–Catenin and p120–Catenin at the OLM of the Rho(–/–) mice, we have also observed intact and normal expression of Alpha–Catenin and E–Cadherin at the OLM of the Rho(–/–) mice, suggesting a distinct involvement of the previous adherens junction associated proteins in the maintenance of OLM integrity.
Upon dissection of neural retinas, we have found, by western blot analysis and real–time PCR, specific increases in expression of the tight/adherens junction associated protein ZO–1 in the neural retina of Rho(–/–) mice concomitant with decreases in expression of Beta–Catenin.
We hypothesise that OLM integrity is affected in conjunction with photoreceptor cell degeneration and these retinal changes may contribute to retinal pathogenesis. Our findings of changes in ZO–1, Beta–Catenin and p120–Catenin expression at the OLM of the Rho(–/–) mice may represent an important therapeutic target with regards to the re–introduction of these proteins to the OLM of degenerating photoreceptors. We believe that the maintenance of OLM integrity may retard or prevent the degeneration of photoreceptors associated with RP.
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