Cytoskeletal involvement in the regulation of aqueous humor outflow.
Cytoskeletal involvement in the regulation of aqueous humor outflow.
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DOI：
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发表时间：
2000-03
影响因子：
4.4
通讯作者：
B. Tian;Benjamin Geiger;David L. Epstein;Paul L. Kaufman
中科院分区：
文献类型：
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作者：
B. Tian;Benjamin Geiger;David L. Epstein;Paul L. Kaufman
前房的液体流动维持眼内压（IOP）和眼球形状，并为无血管化的角膜、晶状体和小梁网（TM）提供氧气和营养。青光眼是一种进行性视神经病变，通常由眼压升高引起，这是由于对经TM和Schlemm管的房水引流的异常高阻力引起的。具有细胞骨架效应的化合物提供了大量长期降低IOP的治疗可能性。目前大多数降低眼压的药物要么抑制房水的产生，要么增加通过睫状肌的流出，从而减少房水通过颞叶的流动，可能损害已经受损的组织，并潜在地压迫角膜和晶状体。青光眼患者通常同时接受几种药物治疗。最近的研究表明，TM细胞骨架可能参与房水流出的调控。直接作用于TM/Schlemm管以减少流出阻力的细胞骨架剂将更符合正常的生理功能，最近的发展表明这种方法正在取得成果。TM的功能组织TM由胶原束阵列组成，胶原束被内皮样细胞覆盖，细胞外物质/基质（ECM）占据了胶原束之间的空间。最外层的近管区或筛网区没有胶原束，但有几个细胞层沉浸在松散的ECM中。邻近的施勒姆管是一条连续的内皮通道，将房水引流至静脉循环。小梁网结构和实验血流研究表明，流动阻力在最外层区域最大，但无论是正常眼还是青光眼，主要阻力屏障的确切位置和性质，以及通过TM和Schlemm管内壁的确切流动路径都不清楚。随着年龄的增长，阻力增加，TM细胞减少，关节旁区ECM发生改变。与年龄匹配的正常人相比，青光眼的TM细胞较少，关节旁ECM出现异常，这表明关节旁的细胞和ECM可能在抵抗调节中起关键作用。细胞的形状、体积、收缩性、与邻近细胞和ECM的粘附性，以及ECM的数量和组成，都可以通过改变流动通道的尺寸或方向来影响阻力，并可能成为降低流动阻力的治疗靶点。
Fluid flow in the anterior chamber maintains intraocular pressure (IOP) and globe shape and supplies oxygen and nutrients to the nonvascularized cornea, lens, and trabecular meshwork (TM). Glaucoma is a progressive optic neuropathy often caused by elevated IOP consequent to abnormally high resistance to aqueous humor drainage via the TM and Schlemm’s canal. Compounds with cytoskeletal effects offer therapeutic possibilities for substantial long-term IOP reduction. Most current IOP-reducing agents either suppress aqueous humor production or increase outflow through the ciliary muscle, thus reducing aqueous humor flow through the TM, perhaps compromising an already compromised tissue and potentially stressing the cornea and lens. Glaucoma patients usually receive several of these agents concurrently. Recent studies indicate that the TM cytoskeleton may be involved in the regulation of aqueous humor outflow. A cytoskeletal agent acting directly on the TM/Schlemm’s canal to reduce outflow resistance would be more consistent with normal physiological function, and recent developments indicate that this approach is moving toward fruition. FUNCTIONAL ORGANIZATION OF THE TM The TM consists of arrays of collagen beams covered by endothelium-like cells, with extracellular material/matrix (ECM) occupying the spaces between the beams. The outermost juxtacanalicular or cribriform region has no collagenous beams but rather several cell layers immersed in loose ECM. The adjacent Schlemm’s canal is a continuous endothelium-lined channel that drains aqueous humor to the general venous circulation. Trabecular meshwork structure and experimental flow studies suggest that flow resistance is maximal in the outermost region, but the exact location and nature of the major resistance barrier, and the exact flow pathways through the TM and the inner wall of Schlemm’s canal, are not clear either in the normal or the glaucomatous eye. With age, resistance increases, TM cells decrease, and alterations of the ECM in the juxtacanalicular region occur. Glaucomatous eyes exhibit fewer TM cells and abnormal-appearing juxtacanalicular ECM compared with age-matched normals, all suggesting that cells and ECM in the juxtacanalicular region may be critical in resistance regulation. Cell shape, volume, contractility, and adhesion to neighboring cells and to the ECM, and amount and composition of the ECM, could affect resistance by altering the dimensions or direction of flow pathways and could be therapeutic targets to reduce flow resistance.