Abstract

Relevance. The relevance of the study lies in the need to clarify the role of DNA repair mechanisms and genomic stress in the pathogenesis of diabetic retinopathy for the search for new therapeutic targets.

Aim. To determine the expression of PMS2 and p53 proteins in the retinal tissues of rats with experimental diabetic retinopathy (DR) and to assess the effects of insulin and the cellular protein kinase blocker sorafenib.

Materials and methods. The study was performed on 50 male Wistar rats. Diabetes mellitus was modelled by a single intraperitoneal injection of streptozotocin (50 mg/kg). After 7 days, animals with persistent hyperglycaemia were randomised into groups: no treatment, insulin treatment, and combined treatment with insulin and sorafenib. Animals were withdrawn from the experiment after 7 days, 28 days, and 3 months. Immunohistochemical examination was performed using antibodies against PMS2 and p53. The proportion of immunopositive cells was determined per 100 cells in 5 fields of view.

Results. In intact animals, PMS2 and p53 immunoreactivity was minimal. During the development of experimental DR, the number of positively stained cells progressively increased. PMS2-positive cells were localised mainly in the ganglion cell layer and plexiform layers of the retina, whereas p53-positive cells were more strongly associated with the vascular bed. Treatment with insulin and sorafenib was accompanied by increased expression of both markers, with the most pronounced effect after combined administration of the drugs. After 3 months, combined therapy increased the proportion of PMS2-positive cells 2.5-fold and p53-positive cells 3.5-fold compared with the control group (p < 0.05).

Conclusions. The development of experimental DR is accompanied by activation of the PMS2- and p53-associated cellular response to DNA damage in retinal tissues. Increased PMS2 expression during treatment with insulin and sorafenib may reflect activation of MMR-associated reparative and adaptive mechanisms. The results support considering PMS2 as a promising marker of genomic stress in diabetic retinopathy.