Rapid Rod Photoreceptor Cell Death Due to Kinesin-2 Dysfunction is Dependent on Apoptosis Triggered by Mislocalized Opsin

Abstract

Purpose: : In rod photoreceptor cells, loss of kinesin-2 function has been shown to cause abnormal accumulations of opsin, arrestin and membranes in the inner segments, and rapid cell death. Using mouse mutants, we sought to identify the underlying cause of the essential perturbation that leads to cell death.

Methods: : Kif3a-

Results: : In Kif3a-null rods, arrestin was found to be mislocalized only in the light, whereupon it colocalized with mislocalized opsin. Nevertheless, neither arrestin nor light was required for cell death. Lowered rod opsin expression provided enhanced photoreceptor cell survival, with an almost complete rescue of cell loss in the total absence of opsin. ERG analysis showed that the retained cones and rods had normal responses. Caspase-3 and c-jun immunoreactivity was correlated with the rate of degeneration.

Conclusions: : Formation of opsin/arrestin complexes was not necessary for eliciting photoreceptor cell death. Our results indicate that the mislocalization of opsin is a major cause of photoreceptor cell death in the absence of kinesin-2, and that the cell death follows a typical apoptotic pathway.

Keywords: photoreceptors • apoptosis/cell death • opsins