Pathomorphological changes in capillaries in streptozotocin-induced diabetes

Abstract

Background. Ophthalmological complications of diabetes mellitus remain a significant medical and social problem worldwide. Considering the aforementioned, diabetic damage to the structures of the eye continues to be a relevant problem as a result of the development of diabetic angiopathy. Aim. The aim of our study was to investigate the structure of blood and lymphatic capillaries and their relationship with the interstitium of the conjunctiva in rats with diabetic angioretinopathy. Methods. The study was conducted on 15 adult, non-pedigree white male rats weighing 120-130 g. Experimental diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (Sigma) at a dose of 7 mg per 100 g of body weight. The development of diabetes was monitored for 2 weeks by measuring blood glucose levels using the glucose oxidase method. The study was performed from the fourth week of the experiment on animals with glucose levels exceeding 15.58 mmol/l. The study included 2 groups of animals: group 1 (10 animals) with developed diabetes mellitus (4 weeks after streptozotocin injection); group 2 (5 animals) served as a control and received injections of 0.9% saline solution for 4 weeks. Samples for ultrastructural analysis were prepared using standard techniques. In the electron histochemical analysis of conjunctival biopsies from rats with streptozotocin-induced diabetes, triglycerides and glycoproteins were investigated using ruthenium red. Results and conclusion. Our research demonstrated that excessive accumulation of carbohydrate-protein fractions from endothelial cells leads to the formation of periepithelial edema. Electron histochemical analysis revealed the presence of a finely granular substance of medium electron density in the periepithelial space, which stained with ruthenium red. This finding indicates an increased content of carbohydrate-protein components. The elevated production of glycosaminoglycans in experimental streptozotocin-induced diabetes is attributed to metabolic disturbances, as endothelial cells are capable of synthesizing elastin, collagen, and glycosaminoglycans. Further, depending on the duration of metabolic disturbances and the progression of the disease with its widening due to significant accumulation of fine-grained ruthenium-positive material. In some capillaries, intensive accumulation of ruthenium-positive material of medium electron density was observed, surrounding the microvessels over a considerable length. The pericapillary space is widened. It accumulates proteins, cellular breakdown products, and triglycerides. Extensive interstitial tissue edema is noted due to the accumulation of glycosaminoglycans and plasma proteins in perivascular spaces, collectively generating high osmotic pressure. Investigating the structural remodeling of blood and lymphatic capillaries and their relationship with the conjunctival interstitium in rats with diabetic angioretinopathy at the end of the fourth week of experimental streptozotocin-induced diabetes will allow for a comparison of the depth of the pathological changes at different time points. This will further contribute to establishing a basis for determining the optimal timeframes, from a morphological perspective, for conducting drug-based correction of changes in eye tissues during the subchronic phase of hyperglycemia. The goal is to stabilize developing and progressively worsening manifestations of diabetic angiopathy.