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R. Funk, B. Rödiger, K. Horling, G. Seigel, E. Kniep, F. Reber; Pharmacological Protection of Neurons Against Damage by Maillard Reaction Intermediates . Invest. Ophthalmol. Vis. Sci. 2003;44(13):132.
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Purpose: The accumulation of Maillard reaction products and intermediates (leading also to advanced glycation endproducts, AGEs) are known to be associated with the risk of diabetic retinopathy and also with retinal damages in glaucoma and AMD. In retinal organ cultures we investigated the damaging effect of such metabolic stress in retinal and CNS neurons using glyoxal and methylglyoxal (reactive intermediates of AGEs). Possible protective effects of dorzolamide and brimonidine were tested by apoptosis assay and microvesicle velocity analysis. Methods: Cultures of retinal E1A and PC 12 cells were incubated (0-24h) with glyoxal and methylglyoxal (0-1mM). Microvesicle movement was documented by video enhanced contrast microscopy and averaged velocities were calculated subsequently. Possible cellular damage was detected immunohistochemically (apoptosis related proteins bax and active-caspase 3) and by flow cytometry (nuclear changes, subG1-peak). In these assays the carbonic anhydrase inhibitor dorzolamide and alpha 2 receptor agonist brimonidine were tested as possible neuroprotectors. Results: After metabolic stress a microvesicle velocity reduction (nearly 50%) was seen which could be prevented by 0,0001 % brimonidine. Brimonidine could diminish the bax and active-caspase 3 reactivity compared to controls. Apoptotic events (50 % of the cells) could be reduced significantly by dorzolamide and brimonidine (20 %). Conclusion: The application of carbonic anhydrase inhibitor dorzolamide and the alpha 2 receptor agonist brimonidine exerts a partial protection of retinal cells in metabolic stress. These anti -glaucomatous drugs induce this positive side effect by a still unknown mechanism.
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