
RESEARCH HIGHLIGHTS Nature Reviews Neuroscience | AOP, published online 10 May 2011; doi:10.1038/nrn3265 –/– NEURODEGENERATIVE DISORDERS and Gnat1 mice that had received rod transplants, but not in untreated Gnat1–/– mice. Transplanted photoreceptors The most important question, however, was whether vision had been see the light improved by transplantation. To test this, the authors monitored whether the Cell transplantation is a possible integration that were 20–30-fold higher transplanted mice reflexively moved treatment strategy for blindness caused than their previous transplantation their heads in the direction of a rotating by retinal degeneration. Although studies. grating. Gnat1–/– mice exhibited no it has been shown that transplanted Morphological and functional head-tracking behaviour, whereas mice photoreceptor cells can differentiate characterization of the integrated cells that had received transplanted rod and acquire a mature photoreceptor showed that they expressed mature photoreceptors did. Furthermore, in a phenotype, whether these cells rod markers and were morphologically visually guided water-maze test — used integrate into retinal circuits to produce similar to wild-type rod photoreceptors. to assess cognitive processing of visual a functional improvement in vision is Like wild-type rods, the transplanted information — only wild-type mice and uncertain. A study by Pearson et al. now cells were located in the outer nuclear Gnat1–/– mice receiving rod transplants demonstrates restored vision in a genetic layer of the retina, and most had synaptic were able to solve the task, whereas mouse model of blindness following boutons expressing rod ribbon synapse untreated Gnat1–/– mice could not. In rod-photoreceptor transplantation. proteins such as ribeye, bassoon and both behavioural tests, performance was The authors used a murine model dystrophin. Wild-type rods form a classic correlated with the number of integrated of stationary night blindness in triad synapse with retinal second-order rod photoreceptors. Overall, these which rod-photoreceptor function bipolar and horizontal cells, and findings show that in mice, at least, retinal had been ablated through knockout ultrastructural analysis confirmed transplantation can restore vision. of α-transducin (GNAT1), a protein transplanted rod photoreceptors to have Sian Lewis essential for phototransduction in formed a similar arrangement. ORIGINAL RESEARCH PAPER Pearson, R. A. et al. these cells. They then harvested rod Next, the authors tested the light Restoration of vision after transplantation of precursor cells for transplantation responses of integrated transplanted photoreceptors. Nature 18 Apr 2012 (doi:10.1038/ from neonatal mouse retinae, having rods using suction-pipette recordings nature10997) identified the cells using green of individual integrated rods. They fluorescent protein as a marker of found that these cells responded to rod photoreceptors (under control of light in a similar way to wild-type rods. the rod-specific transcription factor They reasoned that if the rods had neural retina-specific leucine zipper properly integrated into retinal circuits, protein (NRL)). The authors used then signals from these cells would be optimized transplantation procedures transmitted to visual cortex. Indeed, that involved subretinal injection of stimulation of each eye using dim the donor cells into both the superior flickering black and white bars on a grey and the inferior retina of Gnat1–/– mice background evoked strong responses and obtained levels of photoreceptor in visual cortex of wild-type mice BRAND X NATURE REVIEWS | NEUROSCIENCE VOLUME 13 | JUNE 2012 © 2012 Macmillan Publishers Limited. All rights reserved.
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