Abstract
The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.
Highlights
Vitamin A is an essential vitamin for vertebrates and must be obtained from dietary sources
Binding of the retinol-binding protein (RBP)-TTR-retinol complex to the plasma membrane receptor stimulated by retinoic acid gene 6 (STRA6) of a target cell releases the vitamin from its carrier and facilitates cellular uptake
During transducin activation the schiff base bond between the opsin molecule and the newly isomerized all-trans-retinal is hydrolyzed. This hydrolysis forms free all-trans-retinal which subsequently becomes reduced to all-trans-retinol and binds to the cytosolic protein cellular retinol-binding protein type-1 (CRBP1) where it is transported out of the photoreceptor cell and back to the RPE for regeneration [69]
Summary
Vitamin A is an essential vitamin for vertebrates and must be obtained from dietary sources. Total vitamin A intake consists of many dietary forms including retinyl esters, β-carotene and free retinol. The various functions of vitamin A are carried out by several metabolically active derivatives including 11-cis-retinal and all-trans-retinoic acid, which are required for vision and transcriptional gene regulation respectively [4,5]. Retinoid therapies have the potential to improve the quality of life in patients suffering from genetic retinal diseases by delaying progressive vision loss. The majority of vitamin A in the mammalian diet is not present in the free retinol form, but instead as both retinyl esters in animal tissues, and carotenoids contained in plant material. Preformed vitamin A, in the form of retinol or retinyl esters, is found almost exclusively in animal goods such as dairy products and organ meats such as liver [7,8]. The intestinal mucosa is the active site for the uptake of free retinol, cleavage of carotenoids, and the hydrolysis of retinyl esters in vertebrates [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
