CONTEMPORARY APPROACHES TO THE DIABETES RETINOPATHY TREATMENT

Introduction. Diabetic retinopathy pathogenesis includes mechanisms of the deterioration of retinal neurons activity, which is expressed in generation of oxidative radicals and local antioxidant potential exhaustion. Also newly created vessels, induced by vessels endothelial growth factor (VEGF) represents the substantially important mechanism of retinopathy genesis.

The aim of investigation. To investigate the state of defensive antioxidant thiol-disulfide and ascorbic acid systems in retinal tissue both in experimental diabetes and under condition of treatment, which included lipoic acid as antioxidant and axitinib as anti-VEGF treatment.

Methods of investigations. In 57 Wistar rats diabetes have been modeled via i. p. streptozotocin administration (50.0 mg/kg, i. p.). In 0.5 months from the moment of streptozotocin injection and during next two months treatment with alpha-lipoic acid (20.0 mg/kg, i. p., daily) and avastin (0.5 mg, intravitreally, monthly) started with the consequent determination of the level of thiols and disulfides in retinal tissue with amperometric method. Also the ascorbic acid (AA) level along with oxidated forms of acid were determined with 2,4-dinitrophenylhydrazine.

Results of investigation. The combined administration of avastin and lipoic acid resulted in the significant increase of thiol groups content when compared with the control group data — by 51.1% (P<0.05). At the same time the level of disulfide groups was reduced by 29.0%, (P<0.05), pertained to such one in control group. The level of restored form of AA was also increased 4.7 times after combined administration of avastin and lipoic acid. Also the level of restored AA exceeded corresponded data in groups with separate administration of avastin and lipoic acid 2.2 and by 2.1 times correspondently (Р<0.05). The total level of AA also exceeded such ones in groups with separate administration of avastin and lipoic acid — 2.0 and by 1.9 times correspondently (Р<0.05).

Conclusions. 1. Streptozotocin-induced diabetes in rats results in the substantial deterioration of the thiol-disulfide and ascorbic acid antioxidative systems in the retina tissue which is in favor for vision disturbances. 2. Avastin administration is followed by the improvement of investigated indices by 18.4–53.3% (P<0,05) pertained to initial level. 3. Alpha lipoic acid produced correction of diabet-induced worsening of investigated indices by up to 54.8% (P<0.05). 4. Combined administration of avastin and lipoic acid is resulted in the potentiation of pharmacological therapeutic effects and corresponded improvement of investigated indices. 5. The combined administration of avastin and lipoic acid is possible to recommend for clinical practice.