Biosignature of Oxidative Stress in the Eye: A New Approach to Treat Retinal Diseases

Friday November 19
Chem. Sci. & Engineering Room 211
10:00 a.m.

Presenter: Dr. Wan Jin Jahng, Michigan Tech UniversityDept. of Biological Sciences

Abstract: The regeneration of the 11-cis-retinyl imine chromophore of rhodopsin during the visual cycle and mechanisms that control this process are central questions in the field of vision research. The retinal pigment epithelium (RPE)-specific protein RPE65 is centrally involved in the isomerization and hydrolysis of all-trans-retinyl esters. We investigated that RPE65 cleavage and potential regulatory mechanisms under oxidative stress conditions. Our results indicate that oxidative stress during the visual cycle results in cleavage of RPE65. RPE is essential for retinoid recycling and phagocytosis of photoreceptors.  Understanding of proteome changes that mediate oxidative stress-induced degeneration of RPE cells may provide further insight into the molecular mechanisms of retinal diseases. In the current study, comparative proteomics has been applied to investigate global changes of RPE proteins under oxidative stress.Proteomic techniques including two dimensional electrophoresis, differential gel electrophoresis (DIGE), tandem time-of-flight (TOF-TOF) mass spectrometry, and fluorescent microscopy were used to identify early protein markers of oxidative stress in the RPE. Two biological models of RPE cells revealed several differentially-expressed proteins that are involved in key cellular processes such as energy metabolism, protein folding, redox homeostasis, cell differentiation, and retinoid metabolism. Our results provide a new perspective on early signaling molecules of redox imbalance in the RPE and putative therapeutic target proteins of eye diseases caused by oxidative stress.

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