Phototransduction Accelerates Photoreceptor Cell Death in a Zebrafish Model

Abstract

Purpose:: Many mutations on the genes of phototransduction signal cascades cause inherited retinal diseases. However, the effect of phototransduction on photoreceptor cell death in such diseases remains unknown. The purpose of our study was to determine whether the phototransduction cascade accelerates photoreceptor cell death in inherited retinal diseases.

Methods:: The zebrafish mutation locus oval (ovl) encodes IFT88, which is involved in transport processes in the connecting cilium, which are essential for outer segment development. This locus causes mislocalization of visual pigments and photoreceptor cell death within 3 days after fertilization. In view of the phenotype, ovl is regarded as an animal model of human inherited retinal diseases. We determined the number of surviving photoreceptors in ovl mutants while rhodopsin and transducin alpha were being suppressed by anti-sense morpholinos. Photoreceptors were visualized in the zebrafish rhodopsin promoter-driven green fluorescent protein (GFP) fish line, and the surviving photoreceptors on the cryosections were counted by using fluorescent microscopy.

Results:: Suppression of rhodopsin or transducin alpha significantly increased the number of surviving photoreceptor cells in the ovl retina 96 hours after fertilization (p<0.005). On the other hand, morpholino injections of wild-type zebrafish did not affect the number of surviving photoreceptor cells.

Conclusions:: Blocking of phototransduction upstream of phosphodiesterase has a protective effect on disease photoreceptors. Under abnormal conditions resulting in visual pigment mislocalization, phototransduction cascades may therefore accelerate photoreceptor cell death.

Keywords: photoreceptors • apoptosis/cell death • transgenics/knock-outs