Mitochondrial function is impaired in the primary visual cortex in an experimental glaucoma model

HVOZDA ARANA, AILEN G.; LASAGNI VITAR, ROMINA M.; REIDES, CLAUDIA G.; CALABRÓ, VALERIA; MARCHINI, TIMOTEO; LERNER, S. FABIÁN; EVELSON, PABLO A.; FERREIRA, SANDRA M.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Año: 2021 vol. 701

0003-9861

Glaucoma is a neurodegenerative disease that affects eye structures and brain areas related to the visual system.Oxidative stress plays a key role in the development and progression of the disease. The aims of the present studywere to evaluate the mitochondrial function and its participation in the brain redox metabolism in an experimentalglaucoma model.3-month-old female Wistar rats were subjected to cauterization of two episcleral veins of the left eye to elevatethe intraocular pressure. Seven days after surgery, animals were sacrificed, the brain was carefully removed andthe primary visual cortex was dissected. Mitochondrial bioenergetics and ROS production, and the antioxidantenzyme defenses from both mitochondrial and cytosolic fractions were evaluated.When compared to control, glaucoma decreased mitochondrial ATP production (23%, p < 0.05), with anincrease in superoxide and hydrogen peroxide production (30%, p < 0.01 and 28%, p < 0.05, respectively),whereas no changes were observed in membrane potential and oxygen consumption rate. In addition, theglaucoma group displayed a decrease in complex II activity (34%, p < 0.01). Moreover, NOX4 expression wasincreased in glaucoma compared to the control group (27%, p < 0.05). Regarding the activity of enzymesassociated with the regulation of the redox status, glaucoma showed an increase in mitochondrial SOD activity(34%, p < 0.05), mostly due to an increase in Mn-SOD (50%, p < 0.05). A decrease in mitochondrial GST activitywas observed (11%, p < 0.05). GR and TrxR activity were decreased in both mitochondrial (16%, p < 0.05 and20%, p < 0.05 respectively) and cytosolic (21%, p < 0.01 and 50%, p < 0.01 respectively) fractions in theglaucoma group. Additionally, glaucoma showed an increase in cytoplasmatic GPx (50%, p < 0.01). In thisscenario, redox imbalance took place resulting in damage to mitochondrial lipids (39%, p < 0.01) and proteins(70%, p < 0.05).These results suggest that glaucoma leads to mitochondrial function impairment in brain visual targets, that isaccompanied by an alteration in both mitochondrial and cytoplasmatic enzymatic defenses. As a consequence ofredox imbalance, oxidative damage to macromolecules takes place and can further affect vital cellular functions.Understanding the role of the mitochondria in the development and progression of the disease could bring upnew neuroprotective therapies.