核黄素—紫外线A巩膜交联对实验性近视的影响研究

发布时间：2018-11-17 19:25

【摘要】：目的近视是发病率最高的眼病之一,近视发病率在全球范围内居高不下,并且呈现快速增长的趋势。近视程度越深,与高度近视相关的眼部并发症如视网膜脱离、视网膜下新生血管、白内障和青光眼等的风险也随之显著上升,这些并发症可引起严重视力下降和不可逆性视力损伤。近视眼巩膜结构发生改变,巩膜干重减少,胶原排列紊乱,直径变细,巩膜抗张力变差。巩膜胶原交联可以使巩膜组织的胶原之间发生共价键重新结合,从而增强巩膜组织的机械性能,增强巩膜的抗牵拉能力,进而阻止眼轴的进一步延长。本研究采用面罩法形觉剥夺制作豚鼠近视模型,并通过核黄素-紫外线A诱导后极部巩膜胶原交联,观察后极部巩膜交联对豚鼠实验性近视的影响研究,有望为临床上近视的根本治疗提供新的可靠方法。方法1.选取3周龄三色豚鼠9只,随机分为正常对照组(NOR组,n=4)和形觉剥夺近视组(FDM组,n=5),FDM组配戴气球制作的面罩,暴露左眼、双耳及口鼻,遮盖右眼,NOR组不做任何处理,右眼为实验眼,分别于遮盖前、遮盖1周、2周进行生物学检测,包括屈光度和眼轴长度。2.选取出生3周的三色豚鼠9只,右眼为实验眼,左眼为自身对照。进行右眼单眼核黄素-紫外线A后极部巩膜胶原交联手术,1周后处死豚鼠,取巩膜做成条带,行巩膜生物力学检测。3.选取出生3周的三色豚鼠25只,由丹阳市吕城镇奥臣实验动物养殖场提供(批号:SCXk(京2013-0007)),屈光度范围在0~+8.00D之间,双眼屈光参差小于2.5D,随机分为空白对照组NOR(n=7)、形觉剥夺组FDM(n=7)、单纯交联组NOR+CL(n=5)和近视交联组FDM+CL(n=6),选取右眼为实验眼,左眼为自身对照眼。NOR组不做任何处理,FDM组进行右眼单眼面罩法形觉剥夺,NOR+CL组只进行右眼单眼核黄素-紫外线A后极部巩膜胶原交联,FDM+CL组先进行右眼单眼核黄素-紫外线A后极部巩膜胶原交联,后进行右眼单眼面罩法形觉剥夺。分别于实验前、遮盖1周、2周、3周、4周进行豚鼠眼球光学生物测量,包括屈光度、眼轴长度和角膜曲率,4周测量结束后,处死豚鼠,每组选取2只行组织病理学检测,其余取巩膜条带行生物力学检测。结果1.面罩法形觉剥夺可以成功制作豚鼠实验性近视模型。形觉剥夺2周可以诱导约-2.50D的近视,眼轴延长约0.2mm,FDM组实验眼(OD)与对照眼(OS)相比,更趋近于近视,双眼屈光参差向近视方向发展,NOR组双眼间无明显差异,FDM组与NOR组相比,双眼屈光参差具有明显差异,有统计学意义。2.核黄素-紫外线A诱导的后极部巩膜胶原交联可以成功诱导巩膜胶原交联,有效增强巩膜的机械性能,巩膜的极限应力和弹性模量增大,极限应变减小。3.核黄素-紫外线A诱导的后极部巩膜胶原交联可以延缓豚鼠实验性近视的进展速度。核黄素-紫外线A交联可以延缓近视屈光度增长约35%。FDM组与其他3组相比,实验眼的眼轴较对侧眼明显延长,差异有统计学意义,而FDM+CL组与NOR组相比,眼轴几乎无明显增长。4组组织病理学检测结果显示,视网膜和RPE细胞未见明显损伤。结论核黄素-紫外线A诱导的后极部巩膜胶原交联可以通过增强巩膜的机械性质进而延缓豚鼠实验性近视的进展速度,且对视网膜和RPE细胞无明显损伤。
[Abstract]:Objective Myopia is one of the highest incidence of eye diseases. The incidence of myopia is high in the world, and the trend of rapid growth is presented. The deeper the degree of myopia, the risk of ocular complications associated with high myopia, such as retinal detachment, new blood vessels in the retina, cataracts and glaucoma, has also increased significantly, which can cause severe visual deterioration and irreversible vision damage. The changes of the scleral structure of the myopia, the decrease of the dry weight of the sclera, the disorder of the alignment of the collagen, the diameter of the sclera, and the deterioration of the tensile force of the sclera. The crosslinking of the scleral collagen can reintegrate the collagen between the scleral tissues, thereby enhancing the mechanical properties of the scleral tissue, enhancing the anti-pulling ability of the sclera, and further preventing further extension of the eye axis. In this study, the model of the guinea pig myopia was made by the mask method, and the collagen cross-linking of the sclera was induced by riboflavin-ultraviolet A, and the effect of the post-pole scleral cross-linking on the experimental myopia in the guinea pigs was studied, and a new and reliable method was expected to be provided for the fundamental treatment of myopia. Method 1. The three-week-old three-color guinea pigs were randomly divided into the normal control group (NOR group, n = 4) and the group (FDM group, n = 5), the FDM group wearing the mask made of the balloon, exposed the left eye, the ears and the mouth nose, covering the right eye, the NOR group did not do any treatment, the right eye was the experimental eye, The biological tests were performed for 1 week and 2 weeks, respectively, prior to the covering, including the power and the eye-axis length. 9 of the three-color guinea pigs at 3 weeks of birth were selected, and the right eye was the experimental eye and the left eye was the self-control. Right-eye single-eye riboflavin-UV-A post-scleral collagen cross-linking operation was performed, and the guinea pig was sacrificed after 1 week, and the sclera was made into a band, and the biomechanical testing of the sclera was performed. 25 guinea pigs were selected to be born for 3 weeks, and the three-color guinea pigs were provided (batch number: SCXk (Beijing 2013-0007)) from the laboratory animal farm in Lutown, Danyang City, and the diopters ranged from 0 to + 8. 00D. The refractive index of the two eyes was less than 2.5D, and was randomly divided into the blank control group (NOR (n = 7) and the group FDM (n = 7). In the simple cross-linked group, NOR + CL (n = 5) and short-term cross-linked group FDM + CL (n = 6), the right eye was selected as the experimental eye and the left eye was the self-control eye. The NOR group did not do any treatment, and the FDM group was deprived of the right-eye single-eye mask method. In the NOR + CL group, only the right-eye single-eye riboflavin-ultraviolet A was cross-linked with the sclera collagen, and the FDM + CL group was first subjected to right-eye single-eye riboflavin-ultraviolet-A posterior-pole scleral collagen cross-linking, and the right eye and the single-eye mask method of the right eye are subjected to the right-eye single-eye mask method. The optical measurements of the guinea pig's eye were performed for 1 week, 2 weeks, 3 weeks and 4 weeks before the experiment, including the diopter, the length of the eye and the curvature of the cornea, and after the end of the 4-week measurement, the guinea pigs were sacrificed. Results 1. The experimental myopia model of the guinea pig can be successfully produced by the mask method. The myopia of about-2.50D can be induced in the 2-week-deprivation, the eye-axis is extended by about 0.2mm, and the experimental eye (OD) of the FDM group is more close to the myopia than the control eye (OS), and the refractive index of the two eyes is developed in the near-sighted direction, and there is no significant difference between the two eyes of the NOR group, and the FDM group is compared with the NOR group, There was a significant difference in the refractive index of the two eyes, and it was of statistical significance. The cross-linking of the scleral collagen induced by riboflavin-ultraviolet A can successfully induce the cross-linking of the sclera, effectively enhance the mechanical properties of the sclera, increase the limit stress and the elastic modulus of the sclera, and decrease the limit strain. The cross-linking of the posterior pole and the sclera induced by riboflavin-ultraviolet A can delay the progression of experimental myopia in the guinea pig. Riboflavin-UV-A cross-linking can delay the growth of myopia by about 35%. Compared with the other three groups, the eye-axis of the experimental eye is significantly longer than that of the other three groups, the difference is of statistical significance, and the group of FDM + CL has no significant increase in the eye axis compared with the NOR group. No significant injury was seen in the retina and RPE cells. Conclusion The cross-linking of the scleral collagen induced by riboflavin-ultraviolet A can delay the progress of experimental myopia in the guinea pig by enhancing the mechanical properties of the sclera, and no obvious damage to the retina and RPE cells.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R778.11

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