3.2 层黏连蛋白及其与病理性近视的关系 层黏连蛋白[17](laminin LN),是胚胎发生时期产生最早的蛋白分子之一,是一种重要的细胞外基质,它起到将巩膜层内及各层间胶原纤维和微纤维连结起来的作用,对维持巩膜的组织结构和功能起到重要作用。巩膜组织中层黏连蛋白合成减少、降解增加或在细胞及巩膜组织中的分布异常均可导致巩膜结构及韧性改变,在眼内压的作用下可导致眼轴加长、巩膜壁变薄等,这些变化可能参与病理性近视的形成过程。因此,研究病理性近视眼巩膜组织中层黏连蛋白的表达量及其细胞和组织分布,对于深入了解病理性近视的形成机制有重要意义。层黏连蛋白的这些特征使得LAMA1基因成为最具吸引力的后选基因。
3.3 原发性开角性青光眼(POAG)与病理性近视的关系 通常认为PM与POAG密切相关[9]。据统计,病理性近视人群的平均眼内压(IOP)比正常人群升高27.8%。POAG、高眼压症通常伴有病理性近视,因此POAG人群病理性近视的发病率较高。20世纪早期,Silling 和 Elshing 指出病理性近视实际上是一种进展较慢、较隐匿的POAG,两者可能被同一等位基因的不同表现型所控制。
本研究结果提示:LAMA1基因在单纯性高度近视眼的巩膜组织中转录水平较单纯开角型青光眼和正常对照组显著降低(P<0.01),但在正常对照组和青光眼组差异无显著性(P>0.05),初步说明LAMA1基因可能仅参与病理性近视的形成,而与POAG无关。但因本实验样本例数较少,故LAMA1基因与POAG的相关性尚需进一步研究。
3.4 LAMA1基因及其与病理性近视的关系 LAMA1基因定位于18p11,位于高度近视基因位点MYP2(18p11.31)的区域内,全长9530 bp,可在全身大多数组织中表达,编码LN α1链[17]。因层黏连蛋白的α1链在维系LN结构和功能上起主要作用,故若LAMA1基因发生突变或表达异常都将对层黏连蛋白的合成、分布、结构和功能有着重要的影响。
本研究表明:被认定为病理性近视候选基因的LAMA1基因,在单纯性高度近视眼的前部巩膜组织中其转录水平较非病理性近视对照组显著降低(P<0.01),进而导致层黏连蛋白合成减少,巩膜结构及韧性改变,眼轴加长、巩膜壁变薄等,参与病理性近视的形成过程,因此,初步判定LAMA1基因与病理性近视具有明显的相关性。但其在转录水平受抑制的机制及如何导致病理性近视的形成乃至LAMA1基因是否是病理性近视的致病基因有待进一步研究。
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