Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

Berkeley – mechentel news – In the study of BM. Gaub et al. of Helen Wills Neuroscience Institute of the University of California, Berkeley, USA, they analyze why most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The authors conclude in the journal PNAS in the december 2014 issue that the results in both large and small animal models of photoreceptor degeneration provide path to clinical translation.(bst)

Autoren: Gaub BM, Berry MH, Holt AE, Reiner A, Kienzler MA, Dolgova N, Nikonov S, Aguirre GD, Beltran WA, Flannery JG, Isacoff EY. Korrespondenz: Helen Wills Neuroscience Institute, University of California, Berkeley, and. Studie: Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells. Quelle: Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5574-83. doi: 10.1073/pnas.1414162111. www.pnas.org/content/111/51/E5574.long