March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Development of Repletion of Intracellular Glutathione, Intact, for AMD and Diabetic Retinopathy, Orally, with Advanced-Glutathione™
Author Affiliations & Notes
  • Harry B. Demopoulos
    Cell.Redox Corp, Elmsford, New York
  • Footnotes
    Commercial Relationships  Harry B. Demopoulos, Cell. Redox Corporation (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5356. doi:
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      Harry B. Demopoulos; Development of Repletion of Intracellular Glutathione, Intact, for AMD and Diabetic Retinopathy, Orally, with Advanced-Glutathione™. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5356.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The need for glutathione (GSH) in Ophthalmology is well known. Its use, however, was delayed because exogenous, ordinary glutathione does not cross cell membranes, and in addition, the unstable thiol undergoes oxidative desulferation, leaving injurious Ophthalmic Acid. We have succeeded in developing an Advanced-Glutathione™ that avoids both issues.

Methods: : AMD and Diabetic Retinopathy display uncontrolled free radical reactions, initiated (1)in AMD by blue light excitation of deposits in RPE, tobacco smoke, and dysfunction of the Complement System, and (2) in Diabetes by hyperglycemia. These destroy intracellular glutathione, causing declines: in Redox Potential, and Antioxidant Defenses of RPE, Neuro-Retina, Endothelial Cells, and Vascular Smooth Muscle. The direct free radical damage includes: peroxidation of membrane lipids and proteins; apoptosis of RPE cells with loss of dependent rods; decreased production of Pigment Epithelium Derived Factor (PEDF); free radical promotion of pathologic angio-genesis and of Matrix Metalloproteinases. We chose as a logical model of long-term, progressive, human losses of intracellular glutathione, non-symptomatic, HIV-positive individuals. Progressive, Human losses are documented in the Peripheral Blood Mononuclear Cells (PBMC's) which correlate with declining Clinical status. We used 3 doses:: 1, 2 and 3 gm/d, orally, in an 8 week period, involving timed phlebotomies to secure the points for Area Under the Curve (AUC) analyses. A total of 10,000 GSH assays were conducted.

Results: : Pharmacokinetics of this drug showed a significant dose-response in rapidly repleting intact glutathione in PBMC's, doubling over baseline; p value 0.0005, based on AUC's. There were no safety issues.

Conclusions: : The drug is planned for Phase 2,3 Clinical Trials in AMD and Diabetic Retinopathy, with proposed End Points that include, among others, the Choroidal Neo Vascularization of AMD, and Proliferative Diabetic Retinopathy. Free Radical Pathology, Oxidative Stress and Glutathione insufficiency promote pathologic angiogenesis.

Keywords: diabetic retinopathy • oxidation/oxidative or free radical damage • neovascularization 

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