Effectiveness and Safety of Tolazoline in the Experimental Myopia Control in Chicks
Sitong Chen, Liyuan Sun, Kai Wang, Mingwei Zhao
Institute of Medical Technology, Peking University Health Science Center, Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing 100044, China
Abstract:Objective: To investigate the efficacy and safety of the adrenergic α-receptor blocker tolazoline in the treatment of experimental myopia in chicks, and explore its mechanism. Methods: In this experimental study, totally 61 6-day-old White Lehorn chickens were randomly divided into form deprivation control group (FDM), tolazoline treatment group after form deprivation (FDM+T100), tolazoline combined with NOS inhibitor L-NAME group after form deprivation (FDM+T100+L-NAME), lens induction control group (LIM), tolazoline treatment group after lens induction (LIM+T100), and tolazoline combined with NOS inhibitor L-NAME group after lens induction (LIM+T100+L-NAME) for effcacy study. Chickens were also divided into blank control group (Blank) and tolazoline treatment group (Blank+T100) for safety study. The experimental intervention was performed on the right eyes of all chicks. Eyes requiring tolazoline (T100) treatment were injected with 12.5 μL tolazoline, eyes requiring tolazoline combined L-NAME (T100+L-NAME) were injected with equal equivalent tolazoline and L-NAME, and the control group was injected with normal saline for 6 days. The diopter and eye biological parameters of each group before and after treatment were recorded and analyzed statistically. In the safety study, ERG examinations were performed on blank group and blank+T100 group. After sacrificing the chicks, the eyeballs were fxed and sliced for TUNEL staining to observe retinal damage. The experimental group and the control group in different myopia model were compared in pairs in this study. The independent samples t-test was used for diopter, vitreous depth, choroid thickness, and axial length which satisfy the normal distribution, and the Mann-Whitney U test was used for the electroretinogram ratio results which did not meet the normal distribution. Results: After 6 days of treatment, in the form deprivation model, the FDM+T100 group had reduced refractive myopia (t=-16.16, P<0.001), reduced amount of axial length growth (t=12.41, P<0.001), and reduced amount of choroidal thickness thinning (t=-2.46, P=0.031) compared to the FDM group. Compared to the FDM+T100 group, the FDM+T100+L-NAME group had increased refractive myopia (t=4.20, P=0.001 ), increased amount of axial length growth (t=-2.33, P=0.033). In the lens induction model, when compared with the LIM group, the refractive diopter was reduced in the LIM+T100 group (t=-5.77, P<0.001), axial length growth was reduced (t=4.19, P<0.001). When compared with the LIM+T100 group, the refractive diopter was increased in the LIM+T100+L-NAME group (t=3.74, P=0.001), and increased amount of axial length growth (t=-3.20, P=0.005). In the safety study, there was no signifcant difference in the diopter, the changes of eyeball biological parameters and ERG right/left eye ratio between the blank control group and the simple tolazoline treatment group. No signifcant apoptosis was found among the groups in TUNEL staining. Conclusions: Tolazoline can effectively delay the diopter and axial progression of experimental myopia in chicks. But this effect was weakened by NOS inhibitor L-NAME. It is suggested that nitric oxide (NO) may also play an important role in the dilation of choroidal blood vessels by tolazoline.
陈思童, 孙丽媛, 王凯, 等. 妥拉唑啉控制雏鸡实验性近视进展的有效性和安全性[J]. 中华眼视光学与视觉科学杂志, 2023, 25(6): 420-426.
Sitong Chen, Liyuan Sun, Kai Wang, et al. Effectiveness and Safety of Tolazoline in the Experimental Myopia Control in Chicks. Chinese Journal of Optometry Ophthalmology and Visual science, 2023, 25(6): 420-426. DOI: 10.3760/cma.j.cn115909-20220411-00139