Altered expression and interaction of adherens junction proteins in the developing OLM of the Rho(-/-) mouse.
Retinitis Pigmentosa (RP) represents a major cause of progressive retinal disease worldwide and comprises a heterogeneous group of inherited diseases that are characterised by primary degeneration of rod photoreceptors and secondary degeneration of cone photoreceptors in the retina. The outer limiting membrane (OLM) which allows for the interaction of photoreceptors with surrounding photoreceptors and Müller cells is compromised in many degenerative retinal diseases. Using indirect immunostaining of retinal cryosections from C-129 Wild Type (WT) and C-129 Rho(-/-) mice, we have determined levels of expression of the adherens junction associated proteins ZO-1, beta-catenin and p120-catenin at the OLM from newborn and 1, 2, 3, 4 and 5-week old animals. We have also used immunoprecipitation analysis to determine changes in the association of E-cadherin with ZO-1, beta-catenin and p120-catenin and the association of alpha-catenin with ZO-1 and beta-catenin at these time points in WT and Rho(-/-) mice. We have found that ZO-1 expression at the OLM is present in WT and Rho(-/-) mice after 2weeks, but that levels of expression at the OLM decrease after this time point in the Rho(-/-) mice. beta-catenin expression in the Rho(-/-) mice became compromised at the OLM after 3 weeks, showing a distinct change in staining pattern after 4 weeks and no staining at the OLM after 5 weeks. Moreover, we have shown that p120-catenin expression is not evident at the OLM of the Rho(-/-) mice at the 4 or 5 week time point. To complement this data, we have performed immunoprecipitation analysis on neural retinal lysates from WT and Rho(-/-) mice and herein report fluctuations in the association of E-cadherin with ZO-1, and beta-catenin, while showing that the interaction of E-cadherin with p120-catenin is not established in the retina of C-129 WT and Rho(-/-) mice until 4 weeks after birth and remains un-changed up to and including 5 weeks after birth. Meanwhile, we report that the association of alpha-catenin with ZO-1 is decreased in retinas of the Rho(-/-) from newborn animals up to and including 5 weeks after birth. We have also shown that the association of alpha-catenin and beta-catenin is not well established in WT and Rho(-/-) mice until at least 5 weeks after birth. We hypothesize that these retinal changes at the OLM may contribute significantly to the pathogenesis of retinal degenerations and may represent a unique therapeutic target for intervention in conditions involving rapid photoreceptor cell death.
Campbell
Matthew
M
Ocular Genetics Unit, Department of Genetics, Trinity College Dublin, Ireland.
Humphries
Marian
M
Kenna
Paul
P
Humphries
Peter
P
Brankin
Brenda
B
D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005136:Eye Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse