Neurodegenrative changes in retina of rats with streptozotocin diabetes under different conditions of experimental treatment

Abstract

Introduction . Diabetic retinopathy pathogenesis includes mechanisms of free radical generation and intensification of lipid peroxidation. It was shown that electrical stimulation (ES) of cerbellar structures as well as administration of delta-sleep inducing peptide (DSIP) is able both to alleviate intensified lipid peroxidation and cause neuroprotective action in neuronal tissue. The aim of research was to investigate the effectiveness of combined usage of DSIP and ES of paleocerebellar cortex upon neurodegenerative manifestations in retina of rats suffered from streptozotocin (STZ)- induced diabetes. Methods of investigations . In Wistar rats diabetes have been modeled via i.p. STZ administration (55,0 mg/kg, i.p.). Electrical stimulations (ES) (100 Hz, 0,25 ms, 80-120 mcA, 2,5 s) of paleocerebellar cortex (V-VII lobules), which have been delivered during ten weeks two times daily (9.00; 19.00), started on 15 th day from the moment of STZ injection. DSIP («Sigma-Aldrich Chemie GmbH», Germany) have been administered every third day during ten weeks in a dosage of 50 mcg/ kg, i.p. Separate group of STZ-treated rats have been provided with combined usage of DSIP and ES in mentioned dosage and regimen during ten weeks. Retinal hemotoxylin eosin painted slices (5 mcm) have been used for light microscopy and calculation of the number of neurons in retinal layers using digital photos. Results have been expressed as number of cells/mm 2 + SEM. Results . Histological investigation of retina of rats with STZ diabetes revealed the net neurons vacuolization, along with edematic and picnotic deteriorations of neurons. Such disturbances were absent in intact rats and also less pronounced in groups of rats treated with DSIP and paleocerebellar ES. In rats with STZ-induced diabetes the outer nuclear layer contained less number of neurons – by 35,4% when compared with the same index in intact animals (P 0,05). The number of neurons in the retinal inner nuclear layer of STZ-treated rats was reduced by 2,2 times pertained to intact rats (P<0,05). In groups of rats with DSIP administration and paleocerebellar ES the reduction was 1,94 and 1,8 times correspondently when compared with the intact rats (P<0,05). Combined usage of DSIP and paleocerebellar ES was followed by the prevalence in number of neurons by 53,1% pertained to the similar index in STZ-treated animals (P<0,05). At the same time the number of neurons in inner nuclear layer was still diminished by 30,8% when compared to intact animals (P<0,05). The number of neurons in retinal ganglionar layer in STZ- treated rats was reduced by 2,1 times in comparison with the similar data in intact rats (P<0,05). The reduction of investigated index by 1,79 and 1,93 times was observed in diabetic rats treated with DSIP and ES correspondently (P<0,05). Combined usage of DSIP and ES in STZ-treated rats was followed by prevalence of the number of neurons by 36,9% when compared to the data in STZ-treated rats (P<0,05). At the same time the investigated index was reduced by 34,4% in comparison with the such one registered in intact animals (P<0,05). Conclusions. 1.The development of STZ-induced diabetes is connected with neurodegenerative changes in retina, which is most pronounced in the outer nuclear layer. 2. The combined usage of DSIP and ES of paleocerebellar cortex is followed by the pronounced neurtoprotective action under condition of experimental STZ- induced diabetes.