Purchase this article with an account.
T. Nakao, M. Tsujikawa; Phototransduction and Photoreceptor Cell Death Are Closely Related in a Zebrafish Model of Autosomal Dominant Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2235.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Many mutations which cause inherited retinal diseases such as retinitis pigmentosa (RP) have been identified. However, the precise mechanism of photoreceptor cell death affected by such diseases remains unknown. We previously demonstrated that photoreceptor cells started to decrease from 5 days after fertilization and that photoreceptor cell death is markedly accelerated by light exposure in Q344X transgenic zebrafish. The purpose of our study was to determine whether phototransduction cascade accelerates photoreceptor cell death in transgenic zebrafish with one of the rhodopsin mutations at position 344 (Q344X), which is associated with autosomal dominant retinitis pigmentosa (ADRP) in human.
Transgenic zebrafish with the rhodopsin Q344X mutation associated with ADRP in human were used for analysis. We determined the number of surviving rod photoreceptors in the Q344X transgenic fish while transducin alpha and the rod cGMP-phosphodiesterase beta subunit (PDE6B) were suppressed with anti-sense morpholinos. We compared the number of surviving photoreceptor cells of the morpholino groups to that of the control groups. 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 means of fluorescent microscopy 5 days after fertilization.
Suppression of transducin significantly increased the number of surviving photoreceptor cells (p = 0.0159, control group: n = 14, average = 25.9, SD = 9.56, morpholino group: n = 15, average = 34.7, SD = 11.3), but suppression of PDE6B markedly accelerated the photoreceptor cell death (p = 0.000787, control group: n = 14, average = 50.6, SD = 18.4, morpholino group: n = 15, average = 30.5, SD = 8.53).
Blocking of phototransduction upstream of phosphodiesterase has a protective effect on photoreceptors affected by ADRP. However, suppression of PDE6B reduces the number of surviving photoreceptor cells in Q344X transgenic zebrafish.
This PDF is available to Subscribers Only