Effect of targeted expression of clusterin in photoreceptor cells on retinal development and differentiation

Clusterin expression is increased in tissues undergoing apoptosis, includin g neurodegenerative retina, but the causal relationships remain to be clari fied. To test the hypothesis that overexpression of clusterin could induce apoptosis in neurons, transgenic mice were generated in which rat clusterin transgene was expressed in photoreceptor cells under the transcriptional c ontrol of the human interphotoreceptor retinoid-binding protein (IRBP) prom oter, Photoreceptor cell death in the resulting transgenic mice was examine d by histology and TUNEL techniques. The expression of the clusterin transg ene was confirmed by in situ hybridization in the photoreceptor cells, and results in a complex pattern of clusterin protein distribution in the retin a. A reduction in apoptotic staining in the transgenic retinas was observed from birth to postnatal day 15. These results suggest that clusterin is no t causally involved in apoptotic mechanisms of photoreceptor cell death, bu t may relate to cytoprotective functions.