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Retinal prosthetics, optogenetics, and chemical photoswitches.
ACS Chem Neurosci 2014; 5(10):895-901AC

Abstract

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind.

Authors+Show Affiliations

Department of Ophthalmology, University of Utah School of Medicine , Salt Lake City, Utah 84132, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25089879

Citation

Marc, Robert, et al. "Retinal Prosthetics, Optogenetics, and Chemical Photoswitches." ACS Chemical Neuroscience, vol. 5, no. 10, 2014, pp. 895-901.
Marc R, Pfeiffer R, Jones B. Retinal prosthetics, optogenetics, and chemical photoswitches. ACS Chem Neurosci. 2014;5(10):895-901.
Marc, R., Pfeiffer, R., & Jones, B. (2014). Retinal prosthetics, optogenetics, and chemical photoswitches. ACS Chemical Neuroscience, 5(10), pp. 895-901. doi:10.1021/cn5001233.
Marc R, Pfeiffer R, Jones B. Retinal Prosthetics, Optogenetics, and Chemical Photoswitches. ACS Chem Neurosci. 2014 Oct 15;5(10):895-901. PubMed PMID: 25089879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinal prosthetics, optogenetics, and chemical photoswitches. AU - Marc,Robert, AU - Pfeiffer,Rebecca, AU - Jones,Bryan, Y1 - 2014/08/08/ PY - 2014/8/5/entrez PY - 2014/8/5/pubmed PY - 2015/11/3/medline KW - Retinal degeneration KW - blindness KW - chemical photoswitches KW - optogenetics KW - prosthetics KW - remodeling KW - reprogramming SP - 895 EP - 901 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 5 IS - 10 N2 - Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/25089879/Retinal_prosthetics_optogenetics_and_chemical_photoswitches_ L2 - https://dx.doi.org/10.1021/cn5001233 DB - PRIME DP - Unbound Medicine ER -