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Photoreceptor cells with profound structural deficits can support useful vision in mice
Journal article   Open access   Peer reviewed

Photoreceptor cells with profound structural deficits can support useful vision in mice

Stewart Thompson, Frederick R Blodi, Swan Lee, Chris R Welder, Robert F Mullins, Budd A Tucker, Steven F Stasheff and Edwin M Stone
Investigative ophthalmology & visual science, Vol.55(3), pp.1859-1866
03/25/2014
DOI: 10.1167/iovs.13-13661
PMCID: PMC3968928
PMID: 24569582
url
https://doi.org/10.1167/iovs.13-13661View
Published (Version of record) Open Access

Abstract

In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting 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. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (Rds(P90)). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Rds(P90) 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 optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that Rds(P90) mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m(2)). Photoreceptors 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.
 Electroretinography Animals Vision, Ocular Male Mice Retinal Degeneration - physiopathology Retinal Photoreceptor Cell Outer Segment - pathology Retinal Degeneration - pathology Disease Models, Animal Retinal Ganglion Cells - pathology

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