Influence of high intensity focused ultrasound irradiating cornea on retinas of living rabbits

Abstract

Background High intensity focused ultrasound (HIFU) is a novel noninvasive technique and it has been used to clinical treatment of solid tumors.However, whether it is safe to cure eye related diseases has not been reported. Objective This study was to explore the influence of HIFU on retinas of living rabbits after the irradiation on cornea, and provide a theoretical basis for the safety of clinical therapy. Methods Forty-one rabbits were involved.The corneal stroma of the right eye was irradiated by HIFU that was fixed in circular shape.The left eye with no treatment served as control group.Six rabbits were sacrificed at day 1, 7, 14, 30, 60 and 90 days after irradiation, respectively.The eyeballs of 3 rabbits were collected for paraffin imbedding.Histological method was then used to evaluate the structure of retina.Immunohistochemistry was used to determine the expression of Nogo-A.TUNEL method was carried out to examine cell apoptosis of different layers of retina.The retina of the rest 3 rabbits were collected to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). The retinal morphology of 5 rabbits were scanned by OCT and retinal thickness was recorded before irradiation and 1, 7, 14, 30, 60 and 90 days after irradiation.The use and care of experimental animals complied with Regulations on the Administration of Experimental Animals from National Ministry of Science and Technology. Results The number of retinal cell layers remained intact in the cornea of living rabbits after HIFU irradiation.The structure of each layer was densely and orderly arranged with clear borders between layers.The histological morphology of retinal tissues were the same among control eyes and experimental eyes at different time points.There was no significant difference in Nogo-A expression among control eyes and experimental eyes at different time points (Fgroup=0.672, P=0.413; Ftime=1.622, P=0.157). No significant difference was obtained in SOD activity and MDA contents among control eyes and experimental eyes at different time points (SOD: Fgroup=0.167, P=0.684; Ftime=0.074, P=0.996.MDA: Fgroup=0.005, P=0.946; Ftime=0.405, P=0.844). No TUNEL positive cell was obtained in each group.The thickness of retinal tissues showed no significant difference among before irradiation and 1, 7, 14, 30, 60 and 90 days after irradiation (F=0.150, P=0.988). Conclusions The irradiation of HIFU on the cornea of living rabbits shows no significant influence on the morphology and bioactive factors of retina.Therefore, the therapeutic application of HIFU irradiation on cornea is safe for retina. Key words: High intensity focused ultrasound; Retina; Superoxide dismutase; Malondialdehyde; Nogo-A