Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) ELISA Kits

Human Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) interaction partners

1. Seven novel mutations expand the spectrum of RPE65-related Leber congenital amaurosis in the Chinese population.

2. Autosomal dominant retinitis pigmentosa (adRP) due to a mutation in the gene encoding RPE65 phenocopied choroideremia. Based on our analysis of the 2-year disease progression in this patient, RPE65 adRP is mild and has a slow rate of disease progression.

3. Volumetric assessment of central 30 degrees visual field sensitivity, V30, is a useful independent measure of retinal function and, in our data, represented the best metric to monitor deterioration of retinal sensitivity in RPE65-associated Leber congenital amaurosis.

4. Early onset flecked retinal dystrophy associated with new compound heterozygous RPE65 variants in two unrelated Japanese patients.

5. Autosomal dominant retinal dystrophy resembling choroideremia can arise from a heterozygous mutation in RPE65. It may manifest with mild disease or be non-penetrant. Awareness of these unusual presentations can facilitate targeted molecular investigation.

6. By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with leber congenital amaurosis (LCA). This approach would be useful for identification of disease-causing mutations of LCA.

7. RPE65 variants are the most prevalent causes of Leber congenital amaurosis in Denmark.

8. Hypomorphic mutations of RPE65 are associated with mild disease in childhood with preservation of good visual acuity into adulthood; they may in rare cases be associated with a flecked retina appearance similar to fundus albipunctatus.

9. Influx of T lymphocytes was associated with retinal pigment epithelium and choroidal thinning and diminished expression of RPE65 mRNA, an essential enzyme of the visual cycle.

10. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans.

11. three Leber congenital amaurosis -associated RPE65 mutants (R91W, Y249C and R515W) undergo rapid proteasomal degradation mediated by the 26 S proteasome non-ATPase regulatory subunit 13.

12. Studies indicate that patients with retinol isomerase RPE65R91W mutation have useful cone-mediated vision in the first decade of life, suggesting partial activity of the mutant RPE65R91W protein.

13. Data show that 4-phenylbutyrate (PBA) displayed a significant synergistic effect on the low temperature-mediated rescue of the mutant isomerase activity of RPE65.

14. Expressions of MDSC, FOXP3+TILs, and CTLA-4 are relative stable after nCRT

15. We showed that miR-410 directly regulates predicted target genes OTX2 and RPE65.

16. Studies indicate that patients consistently reported improvement in their vision following delivery of recombinant adenoassociated virus (rAAV) that carried retinal pigment epithelium 65 protein (REP65) gene.

17. All RPE65-mutant observers have consistent and substantial losses in temporal acuity and sensitivity compared with normal observers.

18. when an amino-terminal fragment (Met(1)-Arg(33)) of the N170K/K297G double mutant of hRPE65 was replaced with the corresponding cRPE65 fragment, the isomerohydrolase activity was further increased to a level similar to that of cRPE65.

19. We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction.

20. properties of disease causing RPE65 with regard to molecular pathogenic mechanism

Mouse (Murine) Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) interaction partners

1. The pathological changes in the inner and outer segments layer of RPE65-/- mice were identified as diffuse hyperreflective changes on optical coherence tomography.

2. Rod a-wave and cone b-wave amplitudes of electroretinograms were increased in Cntf (-/-) mice, but rod b-wave amplitudes were unchanged compared with those in WT mice. Up-regulated RPE65 and LRAT levels accelerated both the visual cycle rate and recovery rate of rod light sensitivity in Cntf (-/-) mice.

3. These results indicate that a toxic gain-of-function induced by the D477G RPE65 substitution may play a role in the pathogenesis of this form of dominant retinitis pigmentosa

4. The present study describes identification of CU239, a novel non-retinoid inhibitor of RPE65, a key enzyme in the visual cycle. Our data demonstrated that CU239 selectively inhibited isomerase activity of RPE65, with IC50 of 6muM.

5. Study describes a mouse model of Leber's Congenital Amaurosis type 2 with mutation in Rpe65 gene. Functional and biochemical studies confirm that vitamin A metabolism and visual processing are disrupted in this model.

6. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration.

7. these observations suggest that D477G acts as a dominant-negative mutant of RPE65 that delays chromophore regeneration.

8. The Leu450Met variant of RPE65 is expressed in C57BL/6 and in many genetically modified mice. It confers significant resistance to light induced retinal degeneration (LIRD).

9. Influx of T lymphocytes was associated with retinal pigment epithelium and choroidal thinning and diminished expression of RPE65 mRNA, an essential enzyme of the visual cycle.

10. the RPE65 protein expression was abnormal

11. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans.

12. properties of disease causing RPE65 with regard to molecular pathogenic mechanism

13. The rd12 lesion is in Rpe65. The rd12 mutant phenotype inherits in a semidominant manner. The effects of the mutant mRNA on visual function may result from inefficient binding to ribosomes for translation.

14. Despite the previously reported upregulation of Cspg5 during retinal degeneration in Rpe65/ mice, no protective effect or any involvement of Cspg5 in disease progression was identified.

15. To recapitulate this event in vivo, we examined tumor formation in NOG mice after subcutaneous injection of iPSCs with or without an iPSC-derived RPE sheet (2.5 x 10(5) RPE cells).

16. Cone-opsin trafficking defects were replicated in Rpe65-/- Rho-/- retina-retinal pigment epithelium cultures.

17. The Rpe65KO and tvrm148 mutations do not complement one another, proving that the tvrm148 mutation occurs in the Rpe65 locus and is the causative lesion driving visual function loss.

18. Aromatic residues in the substrate cleft of RPE65 protein govern retinol isomerization and modulate its progression.

19. a role for MYO7A in the translocation of RPE65

20. Rpe65 deficiency may have many metabolic consequences in the underlying neuroretina. Glb1l3 was the only Glb-related member strongly downregulated in Rpe65(-/-) retinas before the onset and during progression of disease.

Fruit Fly (Drosophila melanogaster) Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) interaction partners

1. study identifies NinaB as a key component for visual pigment production and provides evidence that chromophore in opsin-deficient photoreceptors can elicit retinal degeneration

2. Beta-carotene is transported to the adult brain, where cellular uptake by NinaD allows cleavage by the NinaB enzyme to produce retinal

3. Data show that carotenoid-isomerooxygenase activity of NinaB is more generally found in insects, and provide physiological evidence that carotenoids such as 11-cis-retinal can promote visual pigment biogenesis in the dark.

Cow (Bovine) Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) interaction partners

1. Data indicate that Structural differences between delipidated and nondelipidated RPE65 uncovered key residues involved in substrate uptake and processing.

2. oxidative stress during the visual cycle results in cleavage of RPE65

3. the enzymatic activity of native RPE65 strongly depends on its membrane binding and phospholipid environment

4. Rpe65 isomerase associates with membranes through an electrostatic interaction with acidic phospholipid headgroups.

5. retinoid binding role for RPE65

6. Quenching of protein fluorescence is used to demonstrate quantitatively that RPE65 functions by binding to and mobilizing the highly hydrophobic all-trans-retinyl esters, allowing them to enter the visual cycle.

7. Rpe65 converts an all-trans-retinyl ester to 11-cis-retinol and has been identified as retinoid isomerase. Mutations in RPE65 are associated with Leber hereditary optic atrophy

8. Data show that RPE65 is a moderately specific retinoid binding protein directed at long chain all-trans-retinyl esters.

9. investigation of metal ions required for the isomerohydrolase activity of RPE65 using the conversion of all-trans-[3H]retinol to 11-cis-[3H]retinol as the measure for isomerohydrolase activity

10. LRAT is not required for isomerase activity beyond synthesis of retinyl-ester substrate, and the association of Rpe65 with membranes is neither dependent upon LRAT nor the result of S-palmitoylation

11. RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species

Zebrafish Retinal Pigment Epithelium-Specific Protein 65kDa (RPE65) interaction partners

1. Here, we developed a zebrafish transgenic model (rpe65a:nfsB-eGFP) that enabled ablation of large swathes of mature RPE. RPE ablation resulted in rapid RPE degeneration, as well as degeneration of Bruch's membrane and underlying photoreceptors. Using this model, we demonstrate for the first time that zebrafish are capable of regenerating a functional RPE monolayer after RPE ablation.

2. these results showed that residue 58 is a primary determinant of isomerization specificity, because the Y58N mutation in RPE65c and its reciprocal N58Y mutation in 13cIMH completely reversed the respective enzyme isomerization product specificities.