Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse.

PURPOSE Apoptosis is the final common pathway for photoreceptors in several forms of retinitis pigmentosa. Recent study has shown that continuous light exposure upregulates low-affinity neurotrophin receptor p75 (p75NTR), which is involved in light-induced photoreceptor apoptosis in rat retina. However, the function of p75NTR in inherited forms of photoreceptor degeneration has not yet been examined. This study was conducted to elucidate the potential role of p75NTR in the rd mouse, one of the best characterized animal models of retinitis pigmentosa. METHODS Double-mutant (rd/rd, p75NTR-/-) mice were crossbred from rd/rd and p75NTR-/- mice. Retinas from control (+/+, p75NTR+/+; rd/rd, p75NTR+/+; rd/rd, p75NTR+/-), and double-mutant (rd/rd, p75NTR-/-) mice were examined by light microscopy and TdT-mediated dUTP nick end labeling (TUNEL) from postnatal day (P)9 through P20. p75NTR mRNA expression in +/+, p75NTR+/+, and rd/rd, p75NTR+/+ mice were examined by real-time PCR analysis. p75NTR protein expression in +/+, p75NTR+/+; rd/rd, p75NTR+/+; and rd/rd, p75NTR-/- mice were examined by immunohistochemistry. RESULTS p75NTR mRNA expression in rd/rd, p75NTR+/+ mice was significantly upregulated compared with +/+, p75NTR+/+ mice at P13 and P20. p75NTR protein expression was observed mainly in Müller glial cells, and its expression was upregulated in the outer nuclear layer during photoreceptor degeneration. However, histochemical analyses showed that the time course of retinal degeneration and the extent of photoreceptor apoptosis in rd/rd, p75NTR-/- double-mutant mice was indistinguishable from that in rd mice carrying functional p75NTR (rd/rd, p75NTR+/+, and rd/rd, p75NTR+/-). CONCLUSIONS These results suggest that in contrast to its role in light-induced photoreceptor degeneration, p75NTR is not essential for apoptosis in the rd mouse.