Yang J L, Neufeld A H, Zorn M B, Hernandez M R
Schepens Eye Research Institute, Boston, MA.
Exp Eye Res. 1993 May;56(5):567-74. doi: 10.1006/exer.1993.1070.
In primary open-angle glaucoma, elevated intraocular pressure is associated with distortion and reorganization of the connective tissue plates of the lamina cribrosa. We have previously postulated that the resident cells of the lamina cribrosa may respond to elevated intraocular pressure by altering the biosynthesis or degradation of extracellular matrix. To determine the response of lamina cribrosa cells to increased pressure, we have compared cultures of human lamina cribrosa cells, from five individuals, maintained under control and pressurized conditions in vitro. Cells from third to fifth passage cultures of human lamina cribrosa subjected to elevated hydrostatic pressure (50 mm Hg) for 7 days changed shape from flat and polygonal to elongated, synthesized and secreted increased amounts of collagen type I as shown by immunofluorescent localization, and exhibited increased mRNA levels of collagen type I (199 +/- 36% of control) (mean +/- S.D.), as determined by slot-blot hybridization. In contrast, beta-actin mRNA levels were unchanged, indicating that the effects of elevated pressure are probably relatively selective. Our data indicate that elevated pressure increases the synthesis of collagen Type I by human lamina cribrosa cells in vitro. In vivo, lamina cribrosa cells may react to changes in their environment by modulating, specifically, changes in the mRNA levels, production, and secretion of extracellular matrix macromolecules. The relationship of these changes in extracellular matrix to those observed in glaucoma remains to be determined.
在原发性开角型青光眼中，眼压升高与筛板结缔组织板的变形和重组有关。我们之前推测，筛板的驻留细胞可能通过改变细胞外基质的生物合成或降解来响应眼压升高。为了确定筛板细胞对压力增加的反应，我们比较了来自五名个体的人筛板细胞在体外对照条件和加压条件下的培养情况。来自人筛板第三代至第五代培养物的细胞在50毫米汞柱的高静水压下处理7天，其形状从扁平多边形变为细长形，通过免疫荧光定位显示合成并分泌了更多的I型胶原蛋白，并且通过狭缝印迹杂交测定，I型胶原蛋白的mRNA水平增加（为对照的199±36%）（平均值±标准差）。相比之下，β-肌动蛋白mRNA水平未改变，表明压力升高的影响可能具有相对选择性。我们的数据表明，体外压力升高会增加人筛板细胞中I型胶原蛋白的合成。在体内，筛板细胞可能通过特异性调节细胞外基质大分子的mRNA水平、产生和分泌的变化来对其环境变化做出反应。这些细胞外基质的变化与青光眼患者中观察到的变化之间的关系仍有待确定。
