Brain mitochondrial function in glaucoma

Abstract

Glaucoma is the second leading cause for blindness worldwide and damages structures in the brain, including the primary visual cortex. The aim was to evaluate the alterations of mitochondrial function in an experimental glaucoma model. Three-month female Wistar rats were divided in two groups (n= 8): glaucoma (GG) in which rats were operated under a microscope by cauterized two of the episcleral veins and control (CG) which received a sham procedure. Seven days after surgery rats were euthanized, brain cortex was separated, and mitochondria were isolated (CICUAL FFyB n° 3314). The following markers were evaluated: oxygen consumption (OC), ATP production, hydrogen peroxide (H2O2) and superoxide anion (O2-) production, the activities of superoxide dismutase (SOD), complex I-III and complex II-III, cardiolipin content, mitochondrial membrane potential, and NADPH oxidase-4 (NOX4) expression. Comparing to CG, GG showed a decrease in ATP production (23 %, p<0.05) and an increase in H2O2 as well as O2- production (28and 30%, respectively, p<0.05). There were no significant differences in complex I-III activity, whereas complex II-III activity was 50 % lower in GG compared to CG (p<0.05). SOD activity was increased in GG compared to CG (33 %, p<0.05). NOX4 expression was increased in GG compared to CG (27 %, p<0.05). No significant differences were found in OC, cardiolipin content, and mitochondrial membrane potential. These results suggest that mitochondrial function is altered in glaucoma, resulting in a decreased capacity to produce ATP and an increased production of H2O2 and O2-. Increase in SOD activity contributes to the increase in H2O2 levels. As NOX4 expression was higher, it could be one of the sources of the increase of reactive oxygen species. 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.