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Stewart Thompson, Frederick R Blodi, Pratibha Singh, XiuYing Liu, Robert Mullins, Budd A Tucker, Steven F Stasheff, Edwin M Stone; Photoreceptor cells with profound structural deficits can support useful vision in mice.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5956.
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© ARVO (1962-2015); The Authors (2016-present)
In animal models of degenerative photoreceptor diseases, there has been some success restoring photoreception by transplanting new stem-cell-derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer-segments, considered critical for photoreceptor cell function. Photoreceptor cells of mice homozygous for the Rds mutation in Peripherin-2 never develop a fully formed outer-segment. The objective of this study was to determine whether photoreceptor cells that lack a fully formed outer-segment could usefully contribute to vision.
Retinal function in wild-type and Rds mice at 90 days of age (RdsP90) was measured by electroretinogram and multielectrode array recording. Visual capabilities were assessed by three distinct visual behavior tests: the optokinetic tracking response; the discrimination based visual water task; and a wheel running based test of vision augmented mobility.
RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In the optokinetic response and visual water task, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running based test showed that RdsP90 mice needed 3-log units brighter luminance than wild-type for vision augmented mobility (10cd/m2).
Photoreceptor cells that lack fully formed outer-segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision.
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