Optogenetic Therapy for Visual Restoration

Sakai, Daiki; Tomita, Hiroshi; Maeda, Akiko

doi:10.3390/ijms232315041

Cited by 18 publications

(18 citation statements)

References 102 publications

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“…Microbial rhodopsins are used as optogenetics tools, and ChR2, ChronosFP, ChrimsonR, and MCO1 have progressed the clinical trial stage for visual restoration. 55 In optogenetics, it is preferred to use red light due to its phototoxicity to cells and tissue permeability, and a spectral red-shift of tools is a strong demand. Figure 6 shows that many microbial rhodopsins contain hydrophobic residues such as L and I at the N/LI switch, except for some Rh-PDEs and HeRs.…”

Section: ■ Discussionmentioning

confidence: 99%

A Novel Color Switch of Microbial Rhodopsin

et al. 2023

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Function of animal and microbial rhodopsins starts by light absorption of the retinal chromophore. The absorption maximum wavelength (λ max ) of rhodopsins is determined by the energy gap between the electronically ground (S 0 ) and first excited (S 1 ) state of the retinal chromophore, and the color tuning mechanism is one of the central topics in rhodopsin research. "Color switches", color-determining residues, are red-and blue-shifting amino acids at the same position in two rhodopsins, whose exchange causes spectral blue-and red-shifts, respectively, in each rhodopsin. As mutation easily destroys elaborate chromophore−protein interactions, the known color switches in microbial rhodopsins are limited; the L/Q switch in C-helix (TM3), the A/TS switch in G-helix (TM7), and the G/P switch in F-helix (TM6). Here, we report a novel color switch of microbial rhodopsins, which is located in D-helix (TM4). In this color switch, the red-and blue-shifting amino acids are Asn (N) and Leu (L)/Ile (I), respectively. As Asn and Leu/Ile are polar and nonpolar amino acids, respectively, and the position is located near the β-ionone ring, the N/LI switch matches the general rule of color tuning by polarity. The N/LI switch is also useful for optogenetics, as many ion-transporting rhodopsins contain blue-shifting amino acids, such as L and I, at that position.

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Section: ■ Discussionmentioning

confidence: 99%

A Novel Color Switch of Microbial Rhodopsin

et al. 2023

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“…125 A few Phase I/II clinical trials of retinal optogenetics for visual restoration have recently been completed and demonstrated general safety of the approach. 126 Clinical translation for cardiac optogenetic therapies has not advanced as quickly as retinal optogenetics as gene and light delivery to the heart is more challenging. 124 Localized injection of nucleic acid delivery vectors to the immune-privileged eye is relatively simple compared to surgical administration of vectors and implantation of optical stimulation devices into the heart.…”

Section: Programmingmentioning

confidence: 99%

Nucleic Acid Delivery Nanotechnologies for In Vivo Cell Programming

Balcorta,

Contreras Guerrero,

Bisht

et al. 2024

ACS Appl. Bio Mater.

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In medicine, it is desirable for clinicians to be able to restore function and imbue novel function into selected cells for therapy and disease prevention. Cells damaged by disease, injury, or aging could be programmed to restore normal or lost functions, such as retinal cells in inherited blindness and neuronal cells in Alzheimer's disease. Cells could also be genetically programmed with novel functions such as immune cells expressing synthetic chimeric antigen receptors for immunotherapy. Furthermore, knockdown or modification of risk factor proteins can mitigate disease development. Currently, nucleic acids are emerging as a versatile and potent therapeutic modality for achieving this cellular programming. In this review, we highlight the latest developments in nanobiomaterials-based nucleic acid therapeutics for cellular programming from a biomaterial design and delivery perspective and how to overcome barriers to their clinical translation to benefit patients.

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“…If the targeted cells are connected to other cell types in the retinal circuit, light also modulates the activity of these cells. Optogenetic therapy can theoretically be applied to all patients with end-stage RP, regardless of genotype [ 309 ].…”

Section: Gene-independent Strategiesmentioning

confidence: 99%

Retinitis Pigmentosa: Current Clinical Management and Emerging Therapies

Nguyen

Moekotte

Plomp

et al. 2023

IJMS

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Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies characterized by the degeneration of rod photoreceptors, followed by the degeneration of cone photoreceptors. As a result of photoreceptor degeneration, affected individuals experience gradual loss of visual function, with primary symptoms of progressive nyctalopia, constricted visual fields and, ultimately, central vision loss. The onset, severity and clinical course of RP shows great variability and unpredictability, with most patients already experiencing some degree of visual disability in childhood. While RP is currently untreatable for the majority of patients, significant efforts have been made in the development of genetic therapies, which offer new hope for treatment for patients affected by inherited retinal dystrophies. In this exciting era of emerging gene therapies, it remains imperative to continue supporting patients with RP using all available options to manage their condition. Patients with RP experience a wide variety of physical, mental and social-emotional difficulties during their lifetime, of which some require timely intervention. This review aims to familiarize readers with clinical management options that are currently available for patients with RP.

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Optogenetic Therapy for Visual Restoration

Cited by 18 publications

References 102 publications

A Novel Color Switch of Microbial Rhodopsin

A Novel Color Switch of Microbial Rhodopsin

Nucleic Acid Delivery Nanotechnologies for In Vivo Cell Programming

Retinitis Pigmentosa: Current Clinical Management and Emerging Therapies

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