Cellular and Subcellular Optogenetic Approaches Towards Neuroprotection and Vision Restoration

Overview

Journal Prog Retin Eye Res

Specialty Ophthalmology

Date 2022 Dec 12

PMID 36503723

Authors

Edward H Wood

Alexander Kreymerman

Tia Kowal

David Buickians

Yang Sun

Stephanie Muscat

Mark Mercola

Darius M Moshfeghi

Jeffrey L Goldberg

Affiliations

Soon will be listed here.

Abstract

Optogenetics is defined as the combination of genetic and optical methods to induce or inhibit well-defined events in isolated cells, tissues, or animals. While optogenetics within ophthalmology has been primarily applied towards treating inherited retinal disease, there are a myriad of other applications that hold great promise for a variety of eye diseases including cellular regeneration, modulation of mitochondria and metabolism, regulation of intraocular pressure, and pain control. Supported by primary data from the authors' work with in vitro and in vivo applications, we introduce a novel approach to metabolic regulation, Opsins to Restore Cellular ATP (ORCA). We review the fundamental constructs for ophthalmic optogenetics, present current therapeutic approaches and clinical trials, and discuss the future of subcellular and signaling pathway applications for neuroprotection and vision restoration.

Citing Articles

Bridging the gap of vision restoration.

Carleton M, Oesch N Front Cell Neurosci. 2024; 18:1502473.

PMID: 39640234 PMC: 11617155. DOI: 10.3389/fncel.2024.1502473.

The ABCs of Stargardt disease: the latest advances in precision medicine.

Zaydon Y, Tsang S Cell Biosci. 2024; 14(1):98.

PMID: 39060921 PMC: 11282698. DOI: 10.1186/s13578-024-01272-y.

Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients.

Sharif N Pharmaceuticals (Basel). 2023; 16(6).

PMID: 37375739 PMC: 10304251. DOI: 10.3390/ph16060791.

References

Polosukhina A, Litt J, Tochitsky I, Nemargut J, Sychev Y, de Kouchkovsky I . Photochemical restoration of visual responses in blind mice. Neuron. 2012; 75(2):271-82. PMC: 3408583. DOI: 10.1016/j.neuron.2012.05.022. View

Sharma A, Spudich J, Doolittle W . Microbial rhodopsins: functional versatility and genetic mobility. Trends Microbiol. 2006; 14(11):463-9. DOI: 10.1016/j.tim.2006.09.006. View

Han X, Boyden E . Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One. 2007; 2(3):e299. PMC: 1808431. DOI: 10.1371/journal.pone.0000299. View

Bamberg E, Tittor J, Oesterhelt D . Light-driven proton or chloride pumping by halorhodopsin. Proc Natl Acad Sci U S A. 1993; 90(2):639-43. PMC: 45719. DOI: 10.1073/pnas.90.2.639. View

Golden J, Erickson-Davis C, Cottaris N, Parthasarathy N, Rieke F, Brainard D . Simulation of visual perception and learning with a retinal prosthesis. J Neural Eng. 2018; 16(2):025003. DOI: 10.1088/1741-2552/aaf270. View

Ivanova E, Hwang G, Pan Z, Troilo D . Evaluation of AAV-mediated expression of Chop2-GFP in the marmoset retina. Invest Ophthalmol Vis Sci. 2010; 51(10):5288-96. PMC: 2939198. DOI: 10.1167/iovs.10-5389. View

Fischer M, Hickey D, Singh M, MacLaren R . Evaluation of an Optimized Injection System for Retinal Gene Therapy in Human Patients. Hum Gene Ther Methods. 2016; 27(4):150-8. DOI: 10.1089/hgtb.2016.086. View

Mecum N, Russell R, Lee J, Sullivan C, Meng I . Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain. Invest Ophthalmol Vis Sci. 2021; 62(14):15. PMC: 8606841. DOI: 10.1167/iovs.62.14.15. View

Das A, Mallya K, Zhao X, Ahmad F, Bhattacharya S, Thoreson W . Neural stem cell properties of Müller glia in the mammalian retina: regulation by Notch and Wnt signaling. Dev Biol. 2006; 299(1):283-302. DOI: 10.1016/j.ydbio.2006.07.029. View

10.

Wang B, Huang M, Shang D, Yan X, Zhao B, Zhang X . Mitochondrial Behavior in Axon Degeneration and Regeneration. Front Aging Neurosci. 2021; 13:650038. PMC: 7982458. DOI: 10.3389/fnagi.2021.650038. View

11.

Grubb M, Burrone J . Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature. 2010; 465(7301):1070-4. PMC: 3196626. DOI: 10.1038/nature09160. View

12.

Byrne L, Khalid F, Lee T, Zin E, Greenberg K, Visel M . AAV-mediated, optogenetic ablation of Müller Glia leads to structural and functional changes in the mouse retina. PLoS One. 2013; 8(9):e76075. PMC: 3785414. DOI: 10.1371/journal.pone.0076075. View

13.

Benowitz L, He Z, Goldberg J . Reaching the brain: Advances in optic nerve regeneration. Exp Neurol. 2016; 287(Pt 3):365-373. DOI: 10.1016/j.expneurol.2015.12.015. View

14.

Chan L, Mahajan V, Tsang S . Genome Surgery and Gene Therapy in Retinal Disorders. Yale J Biol Med. 2017; 90(4):523-532. PMC: 5733860. View

15.

Tochitsky I, Polosukhina A, Degtyar V, Gallerani N, Smith C, Friedman A . Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells. Neuron. 2014; 81(4):800-13. PMC: 3933823. DOI: 10.1016/j.neuron.2014.01.003. View

16.

Kansara V, Muya L, Wan C, Ciulla T . Suprachoroidal Delivery of Viral and Nonviral Gene Therapy for Retinal Diseases. J Ocul Pharmacol Ther. 2020; 36(6):384-392. PMC: 7404827. DOI: 10.1089/jop.2019.0126. View

17.

Deisseroth K, Feng G, Majewska A, Miesenbock G, Ting A, Schnitzer M . Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci. 2006; 26(41):10380-6. PMC: 2820367. DOI: 10.1523/JNEUROSCI.3863-06.2006. View

18.

Hulliger E, Hostettler S, Kleinlogel S . Empowering Retinal Gene Therapy with a Specific Promoter for Human Rod and Cone ON-Bipolar Cells. Mol Ther Methods Clin Dev. 2020; 17:505-519. PMC: 7114634. DOI: 10.1016/j.omtm.2020.03.003. View

19.

Gradinaru V, Thompson K, Zhang F, Mogri M, Kay K, Schneider M . Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci. 2007; 27(52):14231-8. PMC: 6673457. DOI: 10.1523/JNEUROSCI.3578-07.2007. View

20.

Yurco P, Cameron D . Responses of Müller glia to retinal injury in adult zebrafish. Vision Res. 2005; 45(8):991-1002. DOI: 10.1016/j.visres.2004.10.022. View