利用转基因小鼠及其形觉剥夺诱导近视模型研究lumican基因突变在高度近视发病机制中的作用

Pathological myopia （PM）is a severe hereditary ocular disease leading to severe loss of visual acuity and blindness, while the etiology of this disease is still unclear so far. Genetic factors and environmental factors could both affect the course of development of PM. While those two factors often be investigated separately in previous studies, it has no reported that how to discuss both two factors together in one research which would better imitate the real situation of pathological myopic patients.And it is still unclear that whether there is any interaction existing between the genetic factors and environmental factors. We plan to suture the eye lid of the transgenic mouse of Lumican gene mutation, in order to make an myopic animal model induced by form deprivation. It would be investigated in the hLUM transgenic mouse model that the axial changes，refractive changes，the level of transcription and translation products of Lumican gene,and the structure of scleral tissue.Results of these above would be discussed to identify the exact correlation between the Lumican gene mutation and the pathogenesis of pathological myopia, and the one between this mutation and the form deprivation myopic animal model as well, hoping that this study could provide a basis of explaination of the pathogenesis of pathological myopia , and offer the possibility of the prevention strategy and even the gene therapy of this disease.

病理性近视是目前导致低视力及致盲的重要遗传性眼病之一，其致病原因至今尚未清楚。病因学研究认为病理性近视发病过程可能受"遗传+环境"双重因素共同影响。但目前对于近视病因学及其发病机制的研究，国内外多处于对遗传或者环境因素独立研究的阶段，将两者结合起来，模拟更接近患者生活工作状态的现实状况的研究尚未见报道，两者间是否存在交互作用等仍有待进一步的探索。本研究组拟利用含有Lumican基因突变的转基因小鼠，建立形觉剥夺性近视近视模型，通过检测动物眼轴和屈光度变化，及其巩膜中Lumican基因编码蛋白的表达水平和其他细胞外基质成分的结构特点，探讨Lumican 基因突变在高度近视发病机制中的作用及与形觉剥夺诱导近视模型的相关性，从而为阐明病理性近视的发病机制、疾病的预防和基因治疗奠定基础。

病理性近视是目前导致低视力及致盲的重要遗传性眼病之一，其致病原因包括遗传因素及环境因素等多个方面。本研究组利用前期已成功建立的人突变lumican基因转基因小鼠动物模型，进一步建立其形觉剥夺性近视动物模型，通过检测动物眼轴、屈光度，巩膜中 lumican 基因相关蛋白和其他细胞外基质成分的表达水平变化，探讨 lumican 基因突变在高度近视发病机制中的作用及与形觉剥夺诱导近视模型的相关性。本课题研究发现，lumican基因表达量在转基因小鼠及其形觉剥夺眼巩膜中表达增加，较对侧眼及未处理眼差异具有统计学意义（P<0.05），而巩膜中I型胶原纤维的表达量增加不明显；其胶原纤维的改变主要表现为排列紊乱，胶原纤维直径变细，空隙增多。Lumican转基因小鼠及其形觉剥夺模型均较野生小鼠表现出眼轴延长，屈光度数向近视方向漂移；lumican基因可能参与了病理性近视的形成机制，提示“基因+环境”双重因素对近视发生发展过程中可能造成交互影响。阐明病理性近视的发生发展过程中lumican基因相关的致病机制，为疾病的预防和基因治疗奠定了一定基础。