Anti-aging effect of simvastatin and telmisartan on retinas and its mechanism in rats

Abstract

Background Statins has prominent roles in regulating lipids, anti-inflammation, autoxidation and protecting vascular endothelial cells.Sartans can promote cell growth and the expression of cytokines.Since the pleiotropic effects of statins and sartans on a variety of cell types, it is inferred that the two medicines can delay retinal aging. Objective This study was to explore the anti-aging effect of simvastatin and telmisartan on the physiological aging of retina. Methods Sixty-six three-month-old healthy SD rats were selected in this study, and 6 of them served as the youth group and the right eyeballs were immediately enucleated.The other rats were raised until 9-month-old in the same conditions and then randomly divided into the simvastatin group, telmisartan group and the control group with 20 rats for each group.The simvastatin of 5 mg/kg and telmisartan of 8 mg/kg were given by intragastric administration once a day in the simvastatin group and the telmisartan group until 17-month-old, and the equal amount of normal saline was used in the control group in the same way.The number of survival rats was 12 in the simvastatin group, 10 in the telmisartan group and 8 in the control group.The right eyes were enucleated after heart perfusion of 4% paraformaldehyde solution for the preparation of retinal paraffin sections.Retinal thickness was measured by pathological examination, and the expressions of the retinal neuron markers, including Thy-1, protein kinase C-α (PKC-α), opsin and rhodopsin, were detected by immunofluorescence technique to evaluate the morphology of retinal ganglion cells (RGCs), bipolar cells as well as the thickness of the outer segment of photoreceptors. Results The retinal structure was clear in the rats of the youth group.However, the RGCs arrangement and inner segment (IS) and outer segment (OS) structure were abnormal in the simvastatin group, the telmisartan group and the control group.Compared with the rats of the youth group, the thickness of outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL) and the total thickness of the aging rats were decreased, and the IS/OS thickness was increased in the simvastatin group and the telmisartan group (all at P<0.01). Thy-1 stain showed that the number of RGCs was reduced in the simvastatin group, telmisartan group and the control group compared with the youth group, and that in the simvastatin group was increased in comparison with the control group (all at P<0.01). PKC-α stain exhibited that the density of bipolar cells was increased but the axon terminal bouton was declined in the simvastatin group, telmisartan group and the control group compared with the youth group, and the axon terminal bouton was declined in the simvastatin group compared with the youth group and the control group (all at P=0.000). Opsin and rhodopsin stains displayed that the OS thickness was increased in the simvastatin group, telmisartan group and the control group compared with the youth group, and that in the telmisartan group was reduced in comparison with the control group (all at P<0.01). Conclusions As SD rat aging, retinal thickness is gradually attenuated and the number of RGCs is gradually declined.Although the density of bipolar cells seem to be unchanged, their synaptic connections are decreased and the OS is thicken.Simvastatin and telmisartan can delay retinal senescence by protecting retinal neurons against aging and thinning thickened OS. Key words: Aging/physiology; Retina/physiopathology; Aged; Eye proteins/drug effect; Neurons/structure; Statins; Sartans; Animal, rats