Increased TRPM-2/clusterin mRNA levels during the time of retinal degeneration in mouse models of retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) is a genetically and clinically heterogeneous group of human disorders that is characterized by diminished retinal function, visual cell loss, and blindness. Elevated levels of TRPM-2/clusterin mRNA, a marker for the apoptotic process, have been reported in retinas from patients with advanced stage RP. In the present study we examine TRPM-2/clusterin expression in two genetically distinct mouse models of RP, the rd (retinal degeneration) and rds (retinal degeneration slow) mice. We establish that in advanced postretinal degenerative stages of the rd mutant the retinal TRPM-2/clusterin mRNA levels are highly elevated, as is seen in the case of human RP. Examination of TRPM-2/clusterin mRNA levels in retina and whole eyes from the rd mouse and morphologically normal controls during the period of retinal degeneration (postnatal days 8–21) in the rd phenotype shows that TRPM-2/clusterin mRNA levels are elevated in the rd animal, and this increase begins just after postnatal day 10 and remains high for the remainder of the time course examined. Northern analysis of rds retina and whole eyes shows a delayed increase in TRPM-2/clusterin mRNA levels relative to the rd profile, coinciding with the known period of rds retinal degeneration (postnatal day 14 to 1 year). In each case, the onset of increased TRPM-2/clusterin mRNA levels coincides with the time of photoreceptor cell death.Key words: retinal degeneration, TRPM-2, clusterin, apoptosis, retinitis pigmentosa.