Engineering Sensitive and Adaptable Artificial Photoreceptors to Restore Vision - NCCR MSE

Engineering Sensitive and Adaptable Artificial Photoreceptors to Restore Vision

Cross section of a degenareted Retinitis pigmentosa retina. The genetically delivered light sensor is produced in the remaining outermost neural cell layer (green). In white, the nuclear layers of the retina.
Cross section of a degenareted Retinitis pigmentosa retina. The genetically delivered light sensor is produced in the remaining outermost neural cell layer (green). In white, the nuclear layers of the retina.

This project shows true interdisciplinary, transversal research: Clinical tests are conducted with light sensitive, molecular systems in partnership with the Friedrich-Miescher Institute of our industry-partner, Novartis. Should the tests be successful, this project could enable blind people to see in black and white again and, eventually, regain their full color vision.

Retinitis pigmentosa (RP) refers to a diverse group of progressive, hereditary diseases of the retina that lead to incurable blindness and affects 2 million people worldwide. Artificial photoreceptors constructed by gene delivery of light-activated channels or pumps (functional molecular modules) to surviving cell types in the remaining retinal circuit have shown to restore photosensitivity in animal models of RP at the level of the retina and cortex as well as behaviourally.

Simply said, in a degenerated macula the first step is missing: there are no more rods and cones that can detect light and subsequently convert light into neural signal. The visual nerves however are intact. In tests with apes and dogs the genetically delivered molecular factories dock successfully with the visual nerve of the eye and are activated by light, producing certain impulses that enables blind animals to see again.

Publications

E. Macé, G. Montaldo, S. Trenholm, C. Cowan, A. Brignall, A. Urban, B. Roska “Whole-Brain Functional Ultrasound Imaging Reveals Brain Modules for Visuomotor Integration“ Neuron 2018, 100(5):1241-1251.e7. [DOI]
A. Drinnenberg, F. Franke, R. K. Morikawa, J. Jüttner, D. Hillier, P. Hantz, A. Hierlemann, R. Azeredo da Silveira, B. Roska “How Diverse Retinal Functions Arise from Feedback at the First Visual Synapse“ Neuron 2018. [DOI]
R. Schubert, S. Trenholm, K. Balint, G. Kosche, C. S. Cowan, M. A. Mohr, M. Munz, D. Martinez-Martin, G. Fläschner, R. Newton, J. Krol, B. G. Scherf, K. Yonehara, A. Wertz, A. Ponti, A. Ghanem, D. Hillier, K. Conzelmann, D. J. MüllerB. Roska “Virus stamping for targeted single-cell infection in vitro and in vivo“ Nat. Biotechnol. 2017. [DOI]
J. M. Daum, O. Keles, S. J. B. Holwerda, H. Kohler, F. M. Rijli, M. Stadler, B. Roska “The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch“ eLife 2017, 6:e31437. [DOI]
D. Hillier, M. Fiscella, A. Drinnenberg, S. Trenholm, S. B. Rompani, Z. Raics, G. Katona, J. Juettner, A. Hierlemann, B. Rozsa, B. Roska “Causal evidence for retina-dependent and -independent visual motion computations in mouse cortex“ Nat. Neurosci. 2017. [DOI]
D. Alsteens, R. Newton, R. Schubert, D. Martinez-Martin, M. Delguste, B. RoskaD. J. Müller “Nanomechanical mapping of first binding steps of a virus to animal cells“ Nat. Nanotechnol. 2016:DOI:10.1038/nnano.2016.228. [DOI]
K. Yonehara1, M. Fiscella, A. Drinnenberg, F. Esposti, S. Trenholm, J. Krol, F. Franke, C. Gross Scherf, A. Kusnyerik, J. Müller, A. Szabo, J. Jüttner, F. Cordoba, A. P. Reddy, J. Németh, Z. Z. Nagy, F. Munier, A. Hierlemann, B. Roska “Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity“ Neuron 2016, 89:177. [DOI]
B. Source, C. Escobedo, Y. Toyoda, M. P. Stewart, C. J. Cattin, R. Newton, I. Banerjee, A. Stettler, B. Roska, S. Eaton, A. A. Hyman, A. Hierlemann, D. J. Müller “Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement“ Nat. Commun. 2015, 6:8872. [DOI] [More Information]
M. Fiscella, F. Franke, K. Farrow, J. Muller, B. Roska, R. A. da Silveira, A. Hierlemann “Visual coding with a population of direction-selective neurons“ J. Neurophysiol. 2015, 114:2485-99. [DOI]
A. Adamantidis, S. Arber, J. S. Bains, E. Bamberg, A. Bonci, G. Buzsaki, J. A. Cardin, R. M. Costa, Y. Dan, Y. Goda, A. M. Graybiel, M. Hausser, P. Hegemann, J. R. Huguenard, T. R. Insel, P. H. Janak, D. Johnston, S. A. Josselyn, C. Koch, A. C. Kreitzer, C. Luscher, R. C. Malenka, G. Miesenbock, G. Nagel, B. Roska, M. J. Schnitzer, K. V. Shenoy, I. Soltesz, S. M. Sternson, R. Y. Tsien, G. G. Turrigiano, K. M. Tye, R. I. Wilson “Optogenetics: 10 years after ChR2 in neurons--views from the community“ Nat. Neurosci. 2015, 18:1202-12. [DOI]
A. Wertz, S. Trenholm, K. Yonehara, D. Hillier, Z. Raics, M. Leinweber, G. Szalay, A. Ghanem, G. Keller, B. Rózsa, K. K. Conzelmann, B. Roska “Single-cell–initiated monosynaptic tracing reveals layer-specific cortical network modules“ Science 2015, 349:70. [DOI] [More Information]
I. Krol, C. P. Alvarez, M. Fiscella, A. Hierlemann, B. Roska, W. Filipowicz “A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture“ Nat. Commun. 2015, 6:7305. [DOI]
J. Krol, B. Roska “Rods Feed Cones to Keep them Alive“ Cell 2015, 161:706-08. [DOI]
T. Szikra, S. Trenholm, A. Drinnenberg, J. Jüttner, Z. Raics, K. Farrow, M. Biel, G. Awatramani, D. A. Clark, J. A. Sahel, R. Azeredo da Silveira, B. Roska “Rods in daylight act as relay cells for cone-driven horizontal cell–mediated surround inhibition“ Nat. Neurosci. 2014, 17:1728. [DOI]
K. Yonehara, B. Roska “Neuroscience: retinal projectome reveals organizing principles of the visual system“ Curr. Biol. 2014, 24:R833-5. [DOI]
T. Cronin, L. H. Vandenberghe, P. Hantz, J. Juttner, A. Reimann, A. E. Kacsó, R. M. Huckfeldt, V. Busskamp, H. Kohler, P. S. Lagali, B. Roska, J. Bennett “Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter“ EMBO Mol. Med. 2014, 6:1175. [DOI]
A. S. Chuong, M. L. Miri, V. Busskamp, G. A. C. Matthews, L. C. Acker, A. T. Sørensen, A. Young, N. C. Klapoetke, M. A. Henninger, S. B. Kodandaramaiah, M. Ogawa, S. B. Ramanlal, R. C. Bandler, B. D. Allen, C. R. Forest, B. Y. Chow, X. Han, Y. Lin, K. M. The, B. Roska, J. A. Cardin, E. S. Boyden “Noninvasive optical inhibition with a red-shifted microbial rhodopsin “ Nat. Neurosci. 2014, 17:1123. [DOI]
V. Busskamp, J. Krol, D. Nelidova, J. Daum, T. Szikra, B. Tsuda, J. Jüttner, K. Farrow, B. Gross Scherf, C. P. Patino Alvarez, C. Genoud, V. Sothilingam, N. Tanimoto, M. Stadler, M. Seeliger, M. Stoffel, W. Filipowicz, B. Roska “miRNAs 182 and 183 Are Necessary to Maintain Adult Cone Photoreceptor Outer Segments and Visual Function“ Neuron 2014, 83:586. [DOI]

Project Leader

Botond Roska

Lab

Roska group @FMI