Hollborn Margrit, Francke Mike, Iandiev Ianors, Bühner Eva, Foja Christian, Kohen Leon, Reichenbach Andreas, Wiedemann Peter, Bringmann Andreas, Uhlmann Susann
Department of Ophthalmology and Eye Clinic, Interdisciplinary Center of Clinical Research (IZKF), University of Leipzig Faculty of Medicine, Leipzig, Germany.
Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1262-73. doi: 10.1167/iovs.07-0879.
To determine early alterations in retinal gene expression in a porcine model of rhegmatogenous retinal detachment.
Local detachment was created in eyes of adult pigs by subretinal application of sodium hyaluronate. The gene expression in control tissues and retinas detached for 24 hours was analyzed with a pig genome microarray. Genes with at least three-fold expression changes were detected in the detached retina and in the attached retinal tissue surrounding the local detachment in situ. Structural alterations of the retina were examined by light and electron microscopy.
Identified were 85 genes that were upregulated and 7 that were downregulated in the detached retina. Twenty-eight genes were identified as upregulated in the nondetached retina of the surgical eyes. The genes upregulated in detached retinas were related to inflammation and immune responses (n = 52), antioxidants and metal homeostasis (n = 7), intracellular proteolysis (n = 6), and blood coagulation/fibrinolysis (n = 4). The upregulation of at least 15 interferon-stimulated genes indicates elevated interferon levels after detachment. Gene expression of blue-sensitive opsin was not detectable in the detached retinal tissue, suggesting an early reduction in phototransduction, especially in blue cones. Electron microscopy revealed an accumulation of microglial cells in the inner retinal tissue and of polymorphonuclear leukocytes in the vessels of detached and peridetached retinas.
Differentially expressed genes in the retina early after experimental detachment are mainly related to inflammation and immune responses, intracellular proteolysis, and protection against oxidative stress. A local immune and inflammatory response may represent a major causative factor for reactive changes in the retina after detachment. The inflammatory response is not restricted to the detached retina but is also observed in the nondetached retina; this response may underlie functional changes in these regions described in human subjects.
确定孔源性视网膜脱离猪模型中视网膜基因表达的早期变化。
通过玻璃酸钠视网膜下注射在成年猪眼中造成局部脱离。使用猪基因组微阵列分析对照组织和脱离24小时的视网膜中的基因表达。在脱离的视网膜以及原位局部脱离周围的附着视网膜组织中检测到表达变化至少三倍的基因。通过光学和电子显微镜检查视网膜的结构改变。
在脱离的视网膜中鉴定出85个上调基因和7个下调基因。在手术眼的未脱离视网膜中鉴定出28个上调基因。脱离视网膜中上调的基因与炎症和免疫反应（n = 52）、抗氧化剂和金属稳态（n = 7）、细胞内蛋白水解（n = 6）以及血液凝固/纤维蛋白溶解（n = 4）有关。至少15个干扰素刺激基因的上调表明脱离后干扰素水平升高。在脱离的视网膜组织中未检测到蓝色敏感视蛋白的基因表达，这表明光转导早期减少，尤其是在蓝色视锥细胞中。电子显微镜显示在视网膜内层组织中有小胶质细胞积聚，在脱离和周边脱离视网膜的血管中有多形核白细胞积聚。
实验性脱离后早期视网膜中差异表达的基因主要与炎症和免疫反应、细胞内蛋白水解以及抗氧化应激有关。局部免疫和炎症反应可能是视网膜脱离后视网膜反应性变化的主要致病因素。炎症反应不仅限于脱离的视网膜，在未脱离的视网膜中也观察到；这种反应可能是人类受试者中这些区域功能变化的基础。
