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.

A Mixture of U.S. Food and Drug Administration–Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness

“…Indeed, both light and circadian daytime have been shown to partially suppress the rod visual cycle, which likely provides protection from light damage during day time 36. Second, metabolic suppression and a decrease in oxidative stress are protective for the retina,37,38 even if direct evidence from light-toxicity experiments is missing. In the absence of normal rod phototransduction, the metabolic suppression at dark-light switch is dysfunctional,34 providing one hypothesis for the subtly increased susceptibility to light damage in Gnat1 knock-out mice.…”

Immunohistochemical Characterization of Connexin43 Expression in a Mouse Model of Diabetic Retinopathy and in Human Donor Retinas

“…The connexin43 spot count was carried out as previously described [ 45 ]. Briefly, the connexin43 image was converted to a binary image and an equal threshold value was applied to all images to reduce the background [ 46 ]. To separate different connexin43 clusters, a watershed binary algorithm was applied.…”

Vinpocetine Protects Against Cerebral Ischemia-Reperfusion Injury by Targeting Astrocytic Connexin43 via the PI3K/AKT Signaling Pathway

“…The astrocytic cultures were divided into five groups: (1) a control group, stimulated with DMSO; (2) an OGD/R group, stimulated with DMSO during OGD/R injury; (3) an OGD/R + Vinp group, stimulated with Vinp (30 µM) (Gedeon Richter Pharmaceutical Co., Ltd., Budapest, Hungary) during OGD/R injury; and (4) an OGD/R + Vinp + LY group, stimulated with LY294002 (20 µM) (ab120243, Abcam, Cambridge, MA, United States) and Vinp during OGD/R injury; (5) OGD/R + Vinp + BKM group, stimulated with BKM120 (2 µM) (S2247, Selleck, Houston, TX, United States). LY and Vinp were dissolved in DMSO at a final concentration of 100 mM (Hong et al, 2013;Takac et al, 2013;Nivison-Smith et al, 2015), and BKM was dissolved in DMSO at a final concentration of 10 mM. As described above, all groups were stimulated with the same volume of DMSO, and for the control group 0.33% DMSO proved to have no obvious toxicity on astrocytes (Supplementary Figure S1B).…”