Protective Effect of a Locked Retinal Chromophore Analog against Light-Induced Retinal Degeneration

Molecular Pharmacology
Songqi GaoBeata Jastrzebska

Abstract

Continuous regeneration of the 11-cis-retinal visual chromophore from all-trans-retinal is critical for vision. Insufficiency of 11-cis-retinal arising from the dysfunction of key proteins involved in its regeneration can impair retinal health, ultimately leading to loss of human sight. Delayed recovery of visual sensitivity and night blindness caused by inadequate regeneration of the visual pigment rhodopsin are typical early signs of this condition. Excessive concentrations of unliganded, constitutively active opsin and increased levels of all-trans-retinal and its byproducts in photoreceptors also accelerate retinal degeneration after light exposure. Exogenous 9-cis-retinal iso-chromophore can reduce the toxicity of ligand-free opsin but fails to prevent the buildup of retinoid photoproducts when their clearance is defective in human retinopathies, such as Stargardt disease or age-related macular degeneration. Here we evaluated the effect of a locked chromophore analog, 11-cis-6-membered ring-retinal against bright light-induced retinal degeneration in Abca4-/-Rdh8-/- mice. Using in vivo imaging techniques, optical coherence tomography, scanning laser ophthalmoscopy, and two-photon microscopy, along with in vitro histologic ...Continue Reading

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Citations

May 23, 2020·Experimental Biology and Medicine·Tanu ParmarBeata Jastrzebska
Dec 15, 2019·International Journal of Molecular Sciences·Joseph T Ortega, Beata Jastrzebska
Nov 7, 2020·Molecular Pharmacology·Joseph T OrtegaBeata Jastrzebska
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pol Fernandez-GonzalezPere Garriga

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