豚鼠离焦诱导近视前后巩膜紫外光-核黄素交联阻止近视进展的疗效对比及机制研究

Myopia is a world-wide health disease, which often causes varying damages of visual nervous system. Its main pathophysiological performances are scleral thinning and axial increase. Previous studies in our team found that scleral cross-linking (CXL) using riboflavin/ UVA can enhance the biomechanical strength of the normal human and rabbit eyes sclera and has no significant impact on rhesus monkeys retina and choroid biological parameters after 1 year postoperatively,and a uniaxial tensile test was used to verify the long-term effectiveness of scleral biomechanical strength enhancement, which is expected to become the new surgical option of treating myopia and other scleral ectasia. Therefore, in the present study, guinea pigs eyes are prepared to be used for scleral (equatorial and Posterior) cross-linking before and after defocus-induced myopia model being established, using refraction examination, biomechanical measurements, light microscopy and electron microscopy, etc. By analyzing the outcomes of above examinations in different groups, this study would try to find out the mechanism of scleral cross-linking using for the prevention of myopia progression and compare the different outcomes of scleral cross-linking applied before and after defocus-induced myopia of guinea pigs, in order to provide necessary experimental basis for scleral CXL as a clinical therapy for progressive myopia in the future.

近视是一种严重威胁全球公共卫生的疾病，常引起不同程度的视觉神经系统损害,其主要病理生理学表现是巩膜变薄和眼轴进行性拉长。本团队前期研究结果显示紫外光-核黄素巩膜胶原交联方法能增强正常尸眼及兔眼巩膜的生物力学强度，并验证了该方法应用于正常恒河猴眼的眼内安全性及增强巩膜生物力学的长期有效性，明确了此方法的临床意义。本课题组在此基础上，拟利用豚鼠眼建立离焦性近视模型，并在近视模型眼构建前及构建后分别行紫外光-核黄素巩膜（赤道部及后极部）胶原交联，对比观察不同时机以及不同照射部位行巩膜交联术后豚鼠眼屈光状态和眼轴长度及组织结构的变化，探讨其巩膜组织生物力学和细胞生物力学的变化特性及与诱导近视相关细胞因子的关系，深入阐明豚鼠离焦近视模型构建前行巩膜紫外光-核黄素巩膜胶原交联与近视模型构建后再干预延缓近视发展的差异所在及作用机制，为开拓该疗法可能应用于临床延缓近视发展的合理时机选择提供客观依据。

近视是一种严重威胁全球公共卫生的疾病，常引起不同程度的视觉神经系统损害，其主要病理生理学表现是巩膜变薄和眼轴进行性拉长。本团队前期研究表明紫外光-核黄素巩膜胶原交联方法能增强正常尸眼及兔眼巩膜的生物力学强度，并验证了该方法应用于恒河猴眼的眼内安全性及增强巩膜生物力学的长期有效性。本课题组在此基础上，进一步利用豚鼠眼建立离焦性近视模型，并在近视模型眼构建前及构建后分别行紫外光-核黄素巩膜胶原交联，对比观察不同时机行巩膜交联术后豚鼠眼屈光状态、眼轴长度、组织结构和巩膜生物力学的变化，探讨紫外光-核黄素巩膜胶原交联对于巩膜细胞生物力学和近视相关细胞因子的影响，深入阐明豚鼠离焦近视模型构建前行巩膜紫外光-核黄素巩膜胶原交联与近视模型构建后再干预延缓近视发展的差异及作用机制。本课题研究发现豚鼠离焦近视模型构建前行紫外光-核黄素巩膜胶原交联与近视模型构建后再干预均能有效抑制近视发展，相同年龄组豚鼠屈光度和眼轴长度的比较提示近视模型构建前交联的豚鼠近视程度更轻，但巩膜组织结构和巩膜生物力学变化无显著差异。紫外光-核黄素巩膜交联可能通过增加巩膜胶原原纤维直径和密度，改善近视眼巩膜胶原纤维排列紊乱，增加巩膜厚度，提升巩膜生物力学刚度，以及影响近视相关细胞因子的表达进而有助于增加巩膜细胞外基质合成、减少降解，从而控制近视巩膜重塑，延缓近视进展。上述结果表明近视发生前较近视发生后行巩膜紫外光-核黄素巩膜胶原交联延缓近视进展的疗效更为显著，解决了该方法控制近视的干预时机问题，为开拓该疗法可能应用于临床延缓近视发展的合理时机选择提供客观依据，并深入阐明了该方法延缓近视发展的作用机制，具有较好的临床应用前景及研发潜力，为该方法未来应用于临床控制进行性近视的发展奠定了扎实的客观实验基础。