Neuromag May 2017 - Page 25

search retinal implants for vision res- toration, and my own master’s the- sis revolving around restoring vision through optogenetics was conducted in the laboratory of Thomas Münch. While all of these methodologies hold merit, including them all is beyond the scope of this article, and therefore the following will focus solely on the op- togenetic approach. The main idea of the optogenetics ap- proach to vision restoration is to re- store the light-transducing element of the visual system by introducing light-sensitive proteins into the ret- ina. One of the first and most widely used proteins is channelrhodopsin-2 (ChR2), which was discovered in the unicellular algae Chlamydomonas reinhardtii (13). These algae primar- ily use this light-sensitive protein as a means to increase photosynthesis: by sensing where light is coming from they can orient and move toward it. relatively precisely expressed into cells in different environments, such as in the retina. This is exactly what the optogenetic method for visual resto- ration strives to do. The concept is to take a biologically derived light-sensi- tive protein and circumvent the failing natural system to activate the remains of the intact visual architecture. At the moment, the optogenetic proteins we have in hand do not afford all the de- tailed responses photoreceptors do, but they do at least grant the ability to catch light once again. Eric James McDermott Catch me a rainbow. Image source: Rachel Andrew (flickr.com) ChR2 is not the only optogenetic pro- tein, for example, Wyk and Kleinlogel (2) developed a novel optogenetic tool called Opto-mGluR6 which report- edly (and supported by my own data) is more light-sensitive than ChR2. Reports show that ChR2 is respon- sive to 1 order of magnitude, or only the uppermost 8.33% intensity levels of the normal dynamic range of hu- mans (11), while Opto-mGluR6 is re- portedly responsive to 4.3 orders of magnitude, or the uppermost 35.8% intensity levels of the normal dynamic range (2). This is important because this expanded range of Opto-mGluR6 allows the retina to respond to lower light levels and not only to the ex- tremely high, rare, and photo-toxic light levels needed to activate ChR2. These light-sensitive proteins can be extracted, replicated, and now can be graduated from the Neural and Behavioural Sciences master’s program in 2016. He is cur- rently a neuroscience PhD candidate in Tübingen. [1] Zihl, J., Von Cramon, D., & Mai, N. (1983). Selective disturbance of movement vision after bilateral brain damage. Brain, 106(2), 313-340. [2] van Wyk, M., Pielecka-Fortuna, J., Löwel, S., & Kleinlogel, S. (2015). Restoring the ON switch in blind retinas: opto-mGluR6, a next- generation, cell-tailored optogenetic tool. PLoS Biology, 13(5), e1002143. [3] Beltran, W. A. (2008). On the Role of CNTF as a Pontential Therapy for Retinal Degeneration: Dr. Jekyll or Mr. Hyde?. In Re- cent Advances in Retinal Degeneration (pp. 45-51). Springer New York. [4] Bainbridge, J. W., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., … & Petersen-Jones, S. (2008). Effect of gene therapy on visual function in Leber’s con- genital amaurosis. New England Journal of Medicine, 358(21), 2231-2239. [5] Krol, J., Busskamp, V., Markiewicz, I., Stadler, M. B., Ribi, S., Richter, J., … & Oertner, T. G. (2010). Characterizing light- regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs. Cell, 141(4), 618-631. [6] Zrenner, E., Bartz-Schmidt, K. U., Benav, H., Besch, D., Bruckmann, A., Gabel, V. P., … & Koch, J. (2011). Subretinal electronic chips allow blind patients to read letters and com- bine them to words. Proceedings of the Roy- al Society of London B: Biological Sciences, 278(1711), 1489-1497. [7] Rizzo, J. F., & Wyatt, J. (1997). REVIEW: Prospects for a Visual Prosthesis. The Neu- roscientist, 3(4), 251-262. [8] Li, T., Lewallen, M., Chen, S., Yu, W., ] Zhang, N., & Xie, T. (2013). Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photo- receptor cells. Cell Research, 23(6), 788-802. [9] Santos‐Ferreira, T., Postel, K., Stutzki, H., Kurth, T., Zeck, G., & Ader, M. (2015). Day- light vision repair by cell transplantation. Stem Cells, 33(1), 79-90. [10] Polosukhina, A., Litt, J., Tochitsky, I., Nemargut, J., Sychev, Y., De Kouchkovsky, I., … & Kramer, R. H. (2012). Photochemical restoration of visual responses in blind mice. Neuron, 75(2), 271-282. [11] Lagali, P. S., Balya, D., Awatramani, G. B., Münch, T. A., Kim, D. S., Busskamp, V., … & Roska, B. (2008). Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nature neuroscience, 11(6), 667-675. [12] Busskamp, V., Duebel, J., Balya, D., Fra- dot, M., Viney, T. J., Siegert, S., … & Biel, M. (2010). Genetic reactivation of cone photo- receptors restores visual responses in reti- nitis pigmentosa. Science, 329(5990), 413- 417. [13] Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., … & Bamberg, E. (2003). Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proceedings of the National Aca d- emy of Sciences, 100(24), 13940-13945. May 2017 | NEUROMAG | 25