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Formation and Clearance of All- <i>Trans</i> -Retinol in Rods Investigated in the Living Primate Eye With Two-Photon Ophthalmoscopy
摘要： PURPOSE. Two-photon excited fluorescence (TPEF) imaging has potential as a functional tool for tracking visual pigment regeneration in the living eye. Previous studies have shown that all-trans-retinol is likely the chief source of time-varying TPEF from photoreceptors. Endogenous TPEF from retinol could provide the specificity desired for tracking the visual cycle. However, in vivo characterization of native retinol kinetics is complicated by visual stimulation from the imaging beam. We have developed an imaging scheme for overcoming these challenges and monitored the formation and clearance of retinol. METHODS. Three macaques were imaged by using an in vivo two-photon ophthalmoscope. Endogenous TPEF was excited at 730 nm and recorded through the eye’s pupil for more than 90 seconds. Two-photon excited fluorescence increased with onset of light and plateaued within 40 seconds, at which point, brief incremental stimuli were delivered at 561 nm. The responses of rods to stimulation were analyzed by using first-order kinetics. RESULTS. Two-photon excited fluorescence resulting from retinol production corresponded to the fraction of rhodopsin bleached. The photosensitivity of rhodopsin was estimated to be 6.88 ± 5.50 log scotopic troland. The rate of retinol clearance depended on intensity of incremental stimulation. Clearance was faster for stronger stimuli and time constants ranged from 50 to 300 seconds. CONCLUSIONS. This study demonstrates a method for rapidly measuring the rate of clearance of retinol in vivo. Moreover, TPEF generated due to retinol can be used as a measure of rhodopsin depletion, similar to densitometry. This enhances the utility of two-photon ophthalmoscopy as a technique for evaluating the visual cycle in the living eye.
关键词： photoreceptors,visual cycle,ophthalmic imaging,pigment regeneration
更新于2025-09-23 15:22:29
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[Essentials in Ophthalmology] Advances in Vision Research, Volume II (Genetic Eye Research in Asia and the Pacific) || Genetics and Susceptibility of Retinal Eye Diseases in India
摘要： As per the World Health Organization, genetic eye disorders are one of the top ten major causes of global ocular health burden. AMD and DR take major share of the adult eye diseases component that particularly affects the neurovascular retina. More than 100 genes are known to cause Mendelian types of retinal degenerations including syndromic and non-syndromic RP, and it is presumed that this constitutes only 60% of all the genes known so far, and the remaining are yet to be identified. The burden of genetic disorders in India is significant, and very many significant genes like RPE65 have been identified with consanguineous autosomal recessive pedigrees obtained from this region.
关键词： Visual cycle,Phototransduction pathway,Stargardt disease,Retinitis pigmentosa,Leber congenital amaurosis
更新于2025-09-23 15:21:21
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Potential Therapeutic Agents Against Retinal Diseases Caused by Aberrant Metabolism of Retinoids
摘要： The retinoid (visual) cycle is a complex enzymatic pathway that operates in the retina for the regeneration of 11-cis-retinal (11-cis-Ral), the inherent visual chromophore indispensable for vision. De?ciencies in the retinoid metabolism are involved in pathologic mechanisms of several forms of retinal diseases including age-related macular degeneration, Stargardt’s disease, and Leber’s congenital amaurosis, for which no effective cures presently exist. Nevertheless, the interference of abnormal retinoid metabolism with chemicals has been considered to be a promising strategy aimed at alleviating these retinal dysfunctions. Moreover, since gene therapy is gaining increasing importance in clinical practice, the modulation of key enzymes implicated with the retinoid cycle at a genetic level will hold great promise for the treatment of patients with degenerative diseases of the retina.
关键词： metabolism,photoreceptor,visual chromophores,retinylamine,RPE65,retinal pigment epithelium,retinoid visual cycle,gene therapy,retinoids
更新于2025-09-04 15:30:14