Publication Date:
2012-04-24
Description:
Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1-/- mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1-/- mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888831/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888831/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pearson, R A -- Barber, A C -- Rizzi, M -- Hippert, C -- Xue, T -- West, E L -- Duran, Y -- Smith, A J -- Chuang, J Z -- Azam, S A -- Luhmann, U F O -- Benucci, A -- Sung, C H -- Bainbridge, J W -- Carandini, M -- Yau, K-W -- Sowden, J C -- Ali, R R -- 082217/Wellcome Trust/United Kingdom -- EY016805/EY/NEI NIH HHS/ -- EY06837/EY/NEI NIH HHS/ -- EY11307/EY/NEI NIH HHS/ -- G03000341/Medical Research Council/United Kingdom -- G0901550/Medical Research Council/United Kingdom -- MR/J004553/1/Medical Research Council/United Kingdom -- NIHR-RP-011-003/Department of Health/United Kingdom -- R01 EY011307/EY/NEI NIH HHS/ -- R01 EY011307-18/EY/NEI NIH HHS/ -- R01 EY016805/EY/NEI NIH HHS/ -- R01 EY016805-07/EY/NEI NIH HHS/ -- Department of Health/United Kingdom -- England -- Nature. 2012 May 3;485(7396):99-103. doi: 10.1038/nature10997.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. rachael.pearson@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22522934" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
GTP-Binding Protein alpha Subunits/deficiency/genetics
;
Light
;
Maze Learning
;
Mice
;
Retinal Bipolar Cells/ultrastructure
;
Retinal Horizontal Cells/ultrastructure
;
Retinal Rod Photoreceptor Cells/cytology/*physiology/radiation
;
effects/*transplantation
;
Transducin/deficiency/genetics
;
Vision, Ocular/*physiology/radiation effects
;
Visual Cortex/physiology/radiation effects
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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