Purchase this article with an account.
Deborah L. Stenkamp, Samuel S. Hunter, Ruth A. Frey, Mariel Ryan; Loss Of Visual Function And Lack Of A Photoreceptor Damage Response In A Zebrafish Model For Age-related Cone Loss. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1808.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Many retinal degenerative diseases related to age are characterized by the loss of cone photoreceptors. We recently reported (Stenkamp et al., IOVS 2008, 49:4631-40) that zebrafish heterozygous for a mutant allele of the sonic hedgehog gene (shh+/-, also known as syu+/-) show reduced retinal shh signaling, and progressive cone loss and cone pattern abnormalities as the fish become senescent. In the present study we test two hypotheses: 1) Cone loss and other abnormalities in the aging shh+/- zebrafish impair visual function; and 2) The retinas of aging shh+/- zebrafish show molecular signatures of a photoreceptor damage response.
A place-preference assay was used to monitor a behavioral indication of photopic visual function. Genes known to respond to acute retinal damage in zebrafish and in mouse were identified by mining existing microarray datasets. Gene expression in aging syu+/- retinas was measured by real-time quantitative RT-PCR (QPCR).
50% of zebrafish carrying the shh(tbx) (point mutation) allele were behaviorally blind at 2.5 yrs of age. This age corresponds to the time of initial histological signs of disruption of the cone mosaic in the shh(tbx)+/- zebrafish (Stenkamp et al., 2008). Data mining generated lists of genes that are differentially expressed following acute photoreceptor damage in both zebrafish and mouse (76 genes), representing the evolutionarily conserved component of the photoreceptor damage response, as well as genes that are differentially expressed following acute damage only in zebrafish or only in mouse, representing non-conserved components. Interestingly, genes in the conserved list, as well as those in the non-conserved lists, were not differentially expressed in blind, 2.5 yr old shh(tbx)+/- retinas as compared to their age-matched shh+/+ siblings.
Our first hypothesis was supported: ongoing shh signaling within the zebrafish retina is required for maintenance of cone photoreceptors and of visual function. However, our second hypothesis was not supported: the retinas of shh+/- zebrafish may not initiate a robust photoreceptor damage response to this chronic condition. This latter finding suggests a role for shh signaling in responding to photoreceptor loss.
This PDF is available to Subscribers Only