Evidence for RPE65-independent Vision in the Cone-dominated Zebrafish Retina

Overview

Journal Eur J Neurosci

Specialty Neurology

Date 2007 Sep 18

PMID 17868371

Citations 37

Authors

Helia B Schonthaler

Johanna M Lampert

Andrea Isken

Oliver Rinner

Andreas Mader

Matthias Gesemann

Vitus Oberhauser

Marcin Golczak

Oliver Biehlmaier

Krzysztof Palczewski

Stephan C F Neuhauss

Johannes von Lintig

Affiliations

Soon will be listed here.

Abstract

An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

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