Abstract
Purpose :
Glutamate excitotoxicity has been implicated as a mechanism for injury and death of retinal cells in many eye diseases, such as maculopathy. Previous studies have suggested a lower risk for maculopathy progression in subjects with high dietary intake of antioxidants.
This study tested the hypothesis that α-lipoic acid (ALA) and phosphatidylserine (PS), bioactive substances contained in Pixel Active HD drug, can reduce glutamate release from synaptosomes (SS) in rat retinal cells in order to assess their neuroprotective role.
Methods :
Glutamatergic SS were purified from rat retinal tissue using the superfusion technique. Once isolated, ALA and PS were added at increasing concentrations either alone or in mixture. SS without any substances were used as controls.
Finally, depolarization of SS was induced by adding 15 KCl mM medium.
The effect of the different substances on glutamate overflow following depolarization was assessed by measuring [3H]D-aspartic acid (D-Asp) release, used as a glutamate radioactive tracer. Radioactivity was quantified using liquid scintillation counting.
The study was in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Results :
The D-Asp overflow induced by depolarization from control rat retinal SS was 1.71±0.22% of the total radioactivity amount (mean ± s.e.m., n=15).
In SS enriched with ALA or PS, a concentration dipendent decrease of depolarization-induced overflow of D-Asp was observed.
At 0.001, 0.01, 0.1, 1, 10μM, D-Asp overflow decreased by 12, 44, 65, 68, 66 %, rispectively, compared to controls, in ALA-enriched SS and by 25, 31, 40, 60, 55 % in PS-enriched SS.
The maximum effect was achieved at ALA 0,1μM (65-70% inhibition) and at PS 1μM (55-60%) showing a better efficacy of ALA.
Finally, ALA and PS were used in combination: ALA 0,2μM + PS 1μM, exactly like the ratio of Pixel Active HD, and ALA 0,001 μM + PS 0,01 μM resulted both in a 60% inhibition of D-Asp overflow induced by depolarization.
Conclusions :
Our results support the hypothesis that ALA and PS are effective neuroprotective agents against glutamate-induced excitotoxicity by reducing glutamate release in the retinal rat SS. The findings of this study suggest that Pixel Active HD could be an effective food supplement for the treatment of retinal degenerative diseases that involve excitotoxicity. Further studies are required to determine its efficacy in vivo.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.