[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process].

Abstract

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration.

Purpose: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250.

Material and methods: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days.

Results: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests.

Conclusion: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.