Article
Molecular and genetic approaches to restore photosensitivity in retinal degeneration
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Authors
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Heinz Wässle
- Max Planck Institut für Hirnforschung, Frankfurt, Germany
| Published: | November 30, 2009 |
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Outline
Text
Inherited degenerations of rods and cones, that result in blindness, affect 1 in 3000 humans worldwide. Mice carrying the retinal denegeration mutation (rd1/rd1) loose nearly all of their photoreceptors while inner retinal neurons and synaptic circuits survive. There are several recent attempts to make these surviving neurons intrinsically photosensitive and thus restore visual functions after photoreceptor degenerations. Bi et al. [1] injected adeno-associated viral vectors (AAV) into the vitreous and transfected inner retinal neurons with a microbial-type rhodopsin, channelrhodopsin2 (ChR2). Ganglion cells expressing ChR2 showed intrinsic light responses. Lagali et al. [2] targeted ChR2 to retinal ON-bipolar cells in rd1/rd1 mice. They showed that about 7% of the bipolar cells were transfected and could elicit stable light responses. In behavioral studies the transfected mice showed visual responses. Lin et al. [3] used AAV injection into the vitreous of rd1/rd1 mice to ectopically express melanopsin. Approximately 10% of the ganglion cells expressed melanopsin and stable light responses could be recorded from these cells. In behavioral studies visual responses were observed.
We crossed a transgenic mouse line, that expresses ChR2 in the central nervous system [4] into an rd1/rd1 background and approximately 30% of the ganglion cells were found to express ChR2. They gave stable light responses at light ON, and their sensitivity was only 30–100 times lower than the photopic cone sensitivity. The visual performance of the mice was tested in a two choice visual discrimination task. It was dependent on the residual number of cones and was not significantly improved by the expression of ChR2 in retinal ganglion cells. We would argue that changing all physiological classes of retinal ganglion cells into ON-cells "confuses" the visual cortex and, therefore, vision is not restored despite of the ganglion cell light responses.
This lecture is available as video recording (Attachment 1 [Attach. 1]).
References
- 1.
- Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron. 2006;50(1):23-33. DOI: 10.1016/j.neuron.2006.02.026
- 2.
- Lagali PS, Balya D, Awatramani GB, Münch TA, Kim DS, Busskamp V, Cepko CL, Roska B. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci. 2008;11(6):667-75. DOI: 10.1038/nn.2117
- 3.
- Lin B, Koizumi A, Tanaka N, Panda S, Masland RH. Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci U S A. 2008;105(41):16009-14. DOI: 10.1073/pnas.0806114105
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- Arenkiel BR, Peca J, Davison IG, Feliciano C, Deisseroth K, Augustine GJ, Ehlers MD, Feng G. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron. 2007;54(2):205-18. DOI: 10.1016/j.neuron.2007.03.005
