Differential expression of photoreceptor-specific proteins during disease and degeneration in the progressive rod-cone degeneration (prcd) retina.

Progressive rod-cone degeneration (prcd) is a late-onset hereditary retinal degeneration characterized by normal development of photoreceptors prior to degeneration and death of visual cells. We reported previously that expression of opsin mRNA and protein decreases prior to visual cell degeneration. To examine the specificity of this reduction, we have used immunocytochemistry to correlate photoreceptor-specific protein expression with visual cell disease progression. Eyes from light-adapted age-matched control and prcd-affected dogs were fixed in paraformaldehyde, embedded in diethylene glycol distearate (DGD) wax, and reacted with antibodies specific to interphotoreceptor retinoid-binding protein (IRBP), S-antigen, opsin, phosducin, gamma-phosphodiesterase (gamma-PDE), and beta 1-transducin. While IRBP expression did not change with disease progression, immunoreactivity to other proteins varied. For S-antigen and opsin, immunoreactivity decreased dramatically with the transition from photoreceptor disease to degeneration; gamma-PDE immunolabeling in rods also decreased, but the reduction was less abrupt. However, for two other proteins (phosducin and beta 1-transducin), immunoreactivity increased initially and was redistributed (particularly to the rod outer segment) in early disease (stage 1). Our results show that there is a differential expression of photoreceptor-specific proteins with disease and degeneration that is not uniform for all the gene products examined; expression can be decreased, altered in distribution or remain unchanged. It is clear that the decrease of opsin expression described previously is not an isolated phenomenon in the progression of prcd, but is part of a more generalized degenerative process which eventually culminates in cell death.