Mìžnarodnij Endokrinologìčnij Žurnal (Sep 2023)
Effect of tyrosine protein kinase blockade on the state of retinal microglia in diabetic retinopathy
Abstract
Background. Impaired homeostasis of the retinal tissue in diabetes primarily involves microglia, which triggers a cascade of inflammatory reactions, one of the main mechanisms of diabetic retinopathy (DR). The purpose of the study was to determine the state of microglia in experimental DR and the effect of the tyrosine protein kinase blocker imatinib. Materials and methods. In 45 three-month-old male Wistar rats, diabetes was simulated by a single injection of streptozotocin (50 mg/kg; Sigma-Aldrich). The rats were divided into 3 groups: controls; short-acting insulin; insulin and imatinib (Grindex, Latvia). Immunohistochemically, CD68-positive cells were detected in the retina, and the levels of ionized calcium-binding adapter molecule 1 (Iba-1) and matrix metalloproteinase 9 (MMP-9) was evaluated by immunoblotting. Results. The retinal content of Iba-1 progressively increased and exceeded the initial level by 2.0 times after 7 days, and by 3.55 times after 28 days (p 0.05). CD68-positive cells in the retina were noted in the vessels of the choroid plexus throughout the observation, from the 14th day — in the dilated venules of the outer plexiform layer (monocytic pool), and from day 28 — diffusely in the parenchyma of the inner layers (microglial pool). The latter had either a rounded or a ramified shape, which corresponded to the morphology of amoeboid (phagocytic) or activated microglia. Tyrosine protein kinase blockade prevented the microglial activation in the retina. Signs of inflammation in the form of retinal MMP-9 increase and fibrotic retinal proliferations were absent on the 28th day when using insulin and imatinib. Conclusions. The blockade of retinal inflammation and microglial activation by imatinib indicated the prospects of tyrosine protein kinases inhibition in DR and substantiated the prospect of further research with the clarification of such an effect on other mechanisms of DR development.
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