Absence of voltage-dependent calcium channels delays photoreceptor degeneration in rd mice.

Retinal degeneration results from the apoptotic cell death of photoreceptors. While mutations in a large number of genes give rise to retinal degeneration, the specific mechanisms are not well understood. One hypothesis involves mediation of apoptosis by high concentrations of intracellular Ca(2+). We used a mouse line that carries the rd mutation but also lacks the major L-type voltage-dependent Ca(2+) channel at the photoreceptor synapse to examine whether this route of Ca(2+) entry plays a role in photoreceptor degeneration. In both experimental and control mice, the photoreceptors degenerate. However, at postnatal days 16, 18, and 21 there is a delay in photoreceptor cell loss in the experimental mice, which lack L-type voltage-dependent Ca(2+) channels, compared to controls. These data indicate that Ca(2+) entry via the L-type voltage-dependent Ca(2+) channel contributes to the mechanisms responsible for photoreceptor cell death in this mouse model of retinitis pigmentosa.