Hvozda Arana Ailen G, Lasagni Vitar Romina M, Reides Claudia G, Calabró Valeria, Marchini Timoteo, Lerner S Fabián, Evelson Pablo A, Ferreira Sandra M
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Buenos Aires, Argentina; CONICET- Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Buenos Aires, Argentina; CONICET- Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina.
Arch Biochem Biophys. 2021 Apr 15;701:108815. doi: 10.1016/j.abb.2021.108815. Epub 2021 Feb 18.
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 study were to evaluate the mitochondrial function and its participation in the brain redox metabolism in an experimental glaucoma model. 3-month-old female Wistar rats were subjected to cauterization of two episcleral veins of the left eye to elevate the intraocular pressure. Seven days after surgery, animals were sacrificed, the brain was carefully removed and the primary visual cortex was dissected. Mitochondrial bioenergetics and ROS production, and the antioxidant enzyme defenses from both mitochondrial and cytosolic fractions were evaluated. When compared to control, glaucoma decreased mitochondrial ATP production (23%, p < 0.05), with an increase 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, the glaucoma group displayed a decrease in complex II activity (34%, p < 0.01). Moreover, NOX4 expression was increased in glaucoma compared to the control group (27%, p < 0.05). Regarding the activity of enzymes associated 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 activity was observed (11%, p < 0.05). GR and TrxR activity were decreased in both mitochondrial (16%, p < 0.05 and 20%, p < 0.05 respectively) and cytosolic (21%, p < 0.01 and 50%, p < 0.01 respectively) fractions in the glaucoma group. Additionally, glaucoma showed an increase in cytoplasmatic GPx (50%, p < 0.01). In this scenario, 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 is accompanied by an alteration in both mitochondrial and cytoplasmatic enzymatic defenses. As a consequence of redox 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 up new neuroprotective therapies.
青光眼是一种神经退行性疾病，会影响与视觉系统相关的眼部结构和脑区。氧化应激在该疾病的发生和发展中起关键作用。本研究的目的是评估实验性青光眼模型中的线粒体功能及其在脑氧化还原代谢中的作用。对3个月大的雌性Wistar大鼠进行左眼两条巩膜静脉烧灼术以升高眼压。术后7天，处死动物，小心取出大脑并解剖初级视觉皮层。评估线粒体生物能量学和活性氧生成，以及线粒体和胞质部分的抗氧化酶防御能力。与对照组相比，青光眼使线粒体ATP生成减少（23%，p<0.05），超氧化物和过氧化氢生成增加（分别为30%，p<0.01和28%，p<0.05），而膜电位和氧消耗率未观察到变化。此外，青光眼组复合物II活性降低（34%，p<0.01）。而且，与对照组相比，青光眼组中NOX4表达增加（27%，p<0.05）。关于与氧化还原状态调节相关的酶活性，青光眼显示线粒体SOD活性增加（34%，p<0.05），主要是由于锰超氧化物歧化酶增加（50%，p<0.05）。观察到线粒体谷胱甘肽S-转移酶活性降低（11%，p<0.05）。青光眼组线粒体（分别为16%，p<0.05和20%，p<0.05）和胞质部分（分别为21%，p<0.01和50%，p<0.01）中的谷胱甘肽还原酶和硫氧还蛋白还原酶活性均降低。此外，青光眼显示细胞质谷胱甘肽过氧化物酶增加（50%，p<0.01）。在这种情况下，发生了氧化还原失衡，导致线粒体脂质（39%，p<0.01）和蛋白质（70%，p<0.05）受损。这些结果表明，青光眼导致脑视觉靶点的线粒体功能受损，同时伴有线粒体和细胞质酶防御的改变。作为氧化还原失衡的结果，对大分子发生氧化损伤，并可能进一步影响重要的细胞功能。了解线粒体在该疾病发生和发展中的作用可能会带来新的神经保护疗法。
