Description
RPE65 (retinal pigment epithelium-specific 65 kDa protein) was first described in 1991 and is a key isomerase in RPE that is largely localized to the smooth endoplasmic reticulum (1,2). The RPE65 gene is located on chromosome 1p31 and the protein is synthesized as 533 amino acids in length with a theoretical molecular weight of 61 kDa, although appearing near 65 kDa in SDS-PAGE (1,3). RPE65 serves an important enzymatic function in the visual cycle in converting all-trans-retinyl esters into 11-cis-retinal (1-6). In the visual cycle, light activates rhodopsin and other visual pigments in the photoreceptor cells (rods and cones), eventually generating all-trans-retinol which is transported to the RPE and converted to the vitamin A-derived chromophore 11-cis-rentinal via RPE65 and is then diffused back to the photoreceptor to continue the cycle (1-6). Although it is still unclear, some studies have suggested that S-palmitoylation post-translational modification of RPE65 is responsible for the stability and anchoring to the RPE membrane and therefore functioning enzymatic activity (1,2).
Given its essential role in the vision cycle, it is understandable that mutations in RPE65 are associated with a variety of inherited retinal dystrophies (1, 3-6). Leber Congenital Amaurosis (LCA) and retinitis pigmentosa (RP) are two of the most common retinal dystrophies associated with bi-allelic RPE65 gene mutations (5,6). In 2017 the FDA approved an in vivo gene therapy for treatment of RPE65-associated diseases (5,6). The drug Voretigene Neparvovec, also called Luxturna, is delivered sub-retinally and transduces RPE cells with cDNA encoding for normal RPE65 to help restore vision (5,6). There are several promising completed and ongoing clinical trials for treating RPE65-associated diseases using gene replacement therapy (5).
References
1. Kiser, P. D., & Palczewski, K. (2010). Membrane-binding and enzymatic properties of RPE65. Progress in retinal and eye research. https://doi.org/10.1016/j.preteyeres.2010.03.002
2. Uppal, S., Poliakov, E., Gentleman, S., & Redmond, T. M. (2019). RPE65 Palmitoylation: A Tale of Lipid Posttranslational Modification. Advances in experimental medicine and biology. https://doi.org/10.1007/978-3-030-27378-1_88
3. Redmond T. M. (2009). Focus on Molecules: RPE65, the visual cycle retinol isomerase. Experimental eye research. https://doi.org/10.1016/j.exer.2008.07.015
4. Saari J. C. (2016). Vitamin A and Vision. Sub-cellular biochemistry. https://doi.org/10.1007/978-94-024-0945-1_9
5. Miraldi Utz, V., Coussa, R. G., Antaki, F., & Traboulsi, E. I. (2018). Gene therapy for RPE65-related retinal disease. Ophthalmic genetics. https://doi.org/10.1080/13816810.2018.1533027
6. Apte R. S. (2018). Gene Therapy for Retinal Degeneration. Cell. https://doi.org/10.1016/j.cell.2018.03.021
Bioinformatics
| Entrez |
Mouse
Human
|
| Uniprot |
Human
Human
Mouse
|
| Product By Gene ID |
6121 |
| Alternate Names |
- All-trans-retinyl-palmitate hydrolase
- BCO family, member 3
- BCO3
- EC 3.1.1.64
- EC:3.1.1.64
- EC:5.3.3.22
- LCA2
- lutein isomerase
- meso-zeaxanthin isomerase
- mRPE65
- p63
- RBP-binding membrane protein
- rd12
- retinal pigment epithelium specific protein 65
- Retinal pigment epithelium-specific 65 kDa protein
- retinal pigment epithelium-specific protein 65kDa
- retinitis pigmentosa 20 (autosomal recessive)
- retinoid isomerohydrolase
- Retinol isomerase
- RP20
- RPE65
- RPE65, retinoid isomerohydrolase
- sRPE65
|
