Gennadiy Moiseyev, MS, PhD Assistant Professor of Research
Mailing Address: 941 Stanton L. Young Blvd., BSEB 302C Oklahoma City, OK 73104	Telephone: (405) 271-5896 ext 48443 Fax: (405) 271-3973
Email: gennadiy-moiseyev@ouhsc.edu

Research Interests

1. Visual pigments of retina photoreceptors consist of 11-cis retinal chromophore covalently attached by Schiff base bonds to opsin proteins. The process of vision is initiated by photochemical reactions in photoreceptors resulting in isomerization of 11-cis retinal chromophores to all-trans retinal. The latter is then reduced to all-trans retinol and transported in retinal pigment epithelium (RPE). The photoisomerisation of retinal in the retina triggers the phototransduction cascade. Efficient recycling of the 11-cis retinal chromophore in rhodopsin is absolutely necessary to support normal vision. This 11-cis retinal chromophore regeneration proceeds through the series of enzymatic reactions of retinoids in the RPE. We study the enzymes of the visual cycle, especially RPE65 protein which is crucial for reverse isomerization of all-trans retinyl ester to 11-cis retinol. Mutations in the RPE 65 gene results in severe retinal degenerations and early-onset blindness. The goal of the work is to establish the physiological role of RPE65 and the mechanism of its action.

Education

Moiseyev G., Takahashi Y., Chen Y., Kim S, Ma JX. RPE65 from cone-dominant chicken is a more efficient isomerohydrolase, compared to that from rod-dominant species. J Biol Chem. 2008 Jan 23 [Epub ahead of print]

Kanan Y., Kasus-Jacobi A., Moiseyev G, Sawyer K., Ma JX, Al-Ubaidi MR. : Retinoid processing in cone and Müller cell lines. Exp Eye Res. 2008 Feb;86(2):344-54.

Sandell L.L., Sanderson B.W., Moiseyev G., Johnson T., Mushegian A., Young K.,  Rey J.P.,  Ma JX, Staehling- Hampton K., Trainor P.A. RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development.  Genes Dev. 2007;21, 113-1124.

Kanan Y., Moiseyev G., Agarwal,  N.,  Ma JX., Al-Ubaidi, MR. Light induces programmed cell death by activating multiple independent proteases in a cone photoreceptor cell line. Invest Ophthalmol Vis Sci. 2007, Jan;48(1):40-51.

Chen Y., Moiseyev G., Takahashi, Ma JX. Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65. FEBS Lett. 2006 Jul 24;580(17):4200-4.

Takahashi, Y., Chen, Y., Moiseyev, G. and Ma, J-X. Two Point Mutations Of RPE65 From Patients With Retinal Dystrophies Decrease The Protein Stability and Abolish The Isomerohydrolase Activity Of RPE65. J. Biol. Chem. 2006. Aug 4;281(31):21820-6.

Moiseyev, G., Takahashi, Y., Chen, Y., Gentleman, S., T.M., Redmond, Crouch, R.K. and Ma, J-X. RPE65 is an Iron(II)-dependent Isomerohydrolase in the Retinoid Visual Cycle. J. Biol. Chem 281, 2835-3840, 2006.

Chen, Y., Moiseyev, G., Takahashi, Y. and Ma, J-X. RPE65 gene delivery restores isomerohydrolase activity and prevents early cone loss in Rpe65-/- mice. Invest. Ophthalmol. Vis. Sci. 47:1177-84, 2006.

Takahashi Y., Moiseyev, G., Chen Y. and Ma J.X. The roles of three palmitoylation  sites of RPE65 in its membrane association and isomerohydrolase activity, Invest Ophthalmol Vis Sci, 2006;47(12):5191-6.

Takahashi, Y., Moiseyev, G., Chen, Y., Ma, J.X. Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium.  FEBS Lett. 579:5414-5418, 2005.

Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B.X., Ma, J.  RPE65 Is The Isomerohydrolase In The Retinois Visual Cycle.  Proc. Natl. Acad. Sci. USA 102:12413- 8, 2005.