Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.
The visual cycle is a process in the retina that replenishes the molecule retinal for its use in vision. Retinal is the chromophore of most visual opsins, meaning it captures the photons to begin the phototransduction cascade. When the photon is absorbed, the 11-cis retinal photoisomerizes into all-trans retinal as it is ejected from the opsin protein. Each molecule of retinal must travel from the photoreceptor cell to the RPE and back in order to be refreshed and combined with another opsin. This closed enzymatic pathway of 11-cis retinal is sometimes called Wald's visual cycle after George Wald (1906–1997), who received the Nobel Prize in 1967 for his work towards its discovery.
In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction
In enzymology, a retinal dehydrogenase, also known as retinaldehyde dehydrogenase (RALDH), catalyzes the chemical reaction converting retinal to retinoic acid. This enzyme belongs to the family of oxidoreductases, specifically the class acting on aldehyde or oxo- donor groups with NAD+ or NADP+ as acceptor groups, the systematic name being retinal:NAD+ oxidoreductase. This enzyme participates in retinol metabolism. The general scheme for the reaction catalyzed by this enzyme is:
Retinal pigment epithelium-specific 65 kDa protein, also known as retinoid isomerohydrolase, is an enzyme of the vertebrate visual cycle that is encoded in humans by the RPE65 gene. RPE65 is expressed in the retinal pigment epithelium and is responsible for the conversion of all-trans-retinyl esters to 11-cis-retinol during phototransduction. 11-cis-retinol is then used in visual pigment regeneration in photoreceptor cells. RPE65 belongs to the carotenoid oxygenase family of enzymes.
Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.
Retinaldehyde-binding protein 1 (RLBP1) also known as cellular retinaldehyde-binding protein (CRALBP) is a 36-kD water-soluble protein that in humans is encoded by the RLBP1 gene.
11-cis retinol dehydrogenase is an enzyme that in humans is encoded by the RDH5 gene.
Crumbs homolog 1 is a protein that in humans is encoded by the CRB1 gene.
Aryl-hydrocarbon-interacting protein-like 1 is a protein that in humans is encoded by the AIPL1 gene.
X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is a protein in the ciliary transition zone that in humans is encoded by the RPGRIP1 gene. RPGRIP1 is a multi-domain protein containing a coiled-coil domain at the N-terminus, two C2 domains and a C-terminal RPGR-interacting domain (RID). Defects in the gene result in the Leber congenital amaurosis (LCA) syndrome and in the eye disease glaucoma.
Tubby-related protein 1 is a protein that in humans is encoded by the TULP1 gene.
Retinol dehydrogenase 11 is an enzyme that in humans is encoded by the RDH11 gene.
Retinol dehydrogenase 8 is an enzyme that in humans is encoded by the RDH8 gene.
Inosine-5'-monophosphate dehydrogenase 1, also known as IMP dehydrogenase 1, is an enzyme that in humans is encoded by the IMPDH1 gene.
Gene therapy using lentiviral vectors was being explored in early stage trials as of 2009.
Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
Retinol dehydrogenase 13 (all-trans/9-cis) is a protein that in humans is encoded by the RDH13 gene. This gene encodes a mitochondrial short-chain dehydrogenase/reductase, which catalyzes the reduction and oxidation of retinoids. The encoded enzyme may function in retinoic acid production and may also protect the mitochondria against oxidative stress. Alternatively spliced transcript variants have been described.
Congenital blindness refers to blindness present at birth. Congenital blindness is sometimes used interchangeably with "Childhood Blindness." However, current literature has various definitions of both terms. Childhood blindness encompasses multiple diseases and conditions present in ages up to 16 years old, which can result in permanent blindness or severe visual impairment over time. Congenital blindness is a hereditary disease and can be treated by gene therapy. Visual loss in children or infants can occur either at the prenatal stage or postnatal stage. There are multiple possible causes of congenital blindness. In general, 60% of congenital blindness cases are contributed from prenatal stage and 40% are contributed from inherited disease. However, most of the congenital blindness cases show that it can be avoidable or preventable with early treatment.
