Brain cortex mitochondrial disfunction in an experimental glaucoma model

ROMINA MAYRA LASAGNI VITAR; CLAUDIA REIDES; SANDRA MARÍA FERRERIA; VALERIA CALABRÓ; FABIÁN LERNER; AILEN GALA HVOZDA ARANA; TIMOTEO MARCHINI; PABLO EVELSON

Congreso; ARVO Annual Meeting 2020.; 2020

Purpose: Glaucoma is the second leading cause of blindness worldwide characterized by a specific pattern of optic nerve head damage, retinal ganglion cells death, and specific brain structure damage, including primary visual cortex. The aims were to evaluate the brain mitochondrial function and antioxidant defenses in an experimental glaucoma model.Methods: Three-month female Wistar rats were divided in two groups (n=8): glaucoma (GG) in which rats were operated under a microscope by cauterizing two of the episcleral veins and control (CG) which received a sham procedure. After 7 days, rats were euthanized, brains cortex were separated, and mitochondria were isolated. The following markers were evaluated: oxygen consumption (OC), ATP production, hydrogen peroxide (H2O2) and superoxide anion (O2-) production, complex I-III, II-III, and IV activities, cardiolipin content, mitochondrial membrane potential, NADPH oxidase-4 (NOX4) expression, protein carbonylation (PC), and antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR), and thioredoxin reductase (TrxR).Results: Compared to CG, GG showed a decrease in ATP production (23%, p<0.05) and an increase in H2O2 and O2- production (28% and 30%, respectively, p<0.05). Complex II-III activity was 60% lower in GG than CG (p<0.01). No significant differences were found in complex I and IV activities. SOD activity was increased in GG (34%, p<0.05), whereas GST, GR, and TrxR activities were decreased in GG (11%, 16% and 20%, respectively, p<0.05). NOX4 expression was higher in GG than CG (27%, p<0.05) as well as protein carbonylation (70%, p<0.05). No significant differences were found in OC, GPx activity, cardiolipin content and mitochondrial membrane potential.Conclusions: These results suggest that in Glaucoma brain mitochondrial function is altered supported by a decreased capacity to produce ATP and an increased production of H2O2 and O2-. Increased NOX4 levels could contribute to the enhanced production of reactive oxygen species. Addiitionally, the decrease of the enzymes that recycle non-enzymatic antioxidant could result in a decrease in these antioxidants, leading to oxidative damage to proteins. The understanding of the role of mitochondria in this pathology is important since its function is essential for neurotransmission, and impact on the neuronal survival pathways.