title: Vinpocetine modulates metabolic activity and function during retinal ischemia.
abstract: Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Sydney, Australia;
authors.forename: Lisa
authors.initials: L
authors.lastname: Nivison-Smith
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand;
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: O'Brien
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand;
authors.forename: Mai
authors.initials: M
authors.lastname: Truong
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand;
authors.forename: Cindy X
authors.initials: CX
authors.lastname: Guo
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Sydney, Australia; Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand; Centre for Eye Health, University of New South Wales, Sydney, Australia; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Kalloniatis
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand m.acosta@auckland.ac.nz.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Acosta
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D004734:Energy Metabolism / Q000187:drug effects*; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005071:Evoked Potentials; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D046509:Tissue Culture Techniques; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014748:Vinca Alkaloids; D018698:Glutamic Acid; C013983:vinpocetine; D007770:L-Lactate Dehydrogenase; D005947:Glucose
keywords: ischemia; lactate dehydrogenase; retina; retinal metabolism; vinpocetine