The effect of oxindole derivatives on the development of late ophthalmologic disorders in streptozotocin-induced diabetes mellitus

I n t r o d u c t i o n . In Russia, as of 2021, 5 million 168.8 thousand patients with diabetes mellitus (DM) were registered. Ophthalmologic late complications of DM (cataract, retinopathy, glaucoma) lead to a progressive decline in vision up to blindness, and, consequently, to a decrease in the quality of life of patients with DM. Prevention of DM complications is directly related to glycemiс control, which is not always possible, therefore, the search for new pharmacological agents for correction of the consequences of DM is an urgent task. In previous studies, among melatonin isosteres, the compound K-165 was synthesized, which has ophthalmic hypotensive properties.

A i m . To study the eff ect of a new melatonin bioisostere, a 3-arylidene-2-oxindole derivative, on diabetic cataractogenesis, intraocular pressure (IOP), retinal microcirculation and functional activity of the retina in streptozotocin-induced DM.

M a t e r i a l s a n d m e t h o d s . DM was modeled by administering streptozotocin (45 mg/kg, DM group) into the tail vein of male Sprague Dawley rats weighing 260–280 g. Throughout the experiment, for 60 days, to reduce the risk of death from ketoacidosis, the experimental animals subcutaneously received biphasic insulin, Humulin M3 (Eli Lilly, France). Since the 61st day of the experiment, the animals were instilled 0.4% solutions of K-165 and melatonin (experimental group and reference drug group). During the experiment, intravital measurements of IOP, ocular microcirculation level and electroretinography were carried out to evaluate the effectiveness of the studied compound. After euthanasia of the animals, the enucleated eyeballs were used for pathomorphological examination and determination of advanced glycation end products and carboxymethyllysine in the lens structures.

R e s u l t s . The compound K-165 in streptozotocin-induced DM reduces the severity of pathomorphological signs of cataract by 32% (defragmentation, swelling in lens fibers, appearance of Morgagni globules) and the level of IOP by 24%, increases the level of ocular blood microperfusion by 37.5% and shows a tendency to increase the combined response of rods and cones.

C o n c l u s i o n . A new derivative of 3-arylidene-2-oxindole, the compound K-165, exhibits a pronounced anti-cataract effect, reduces the level of IOP in animals with experimental DM, improves microcirculation parameters and demonstrates a tendency to normalize the bioelectrical activity of the retina, and has a neuroprotective eff ect on the retina.

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