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Abstract #5586 Published in IGR 2-1
Cytoskeletal involvement in the regulation of aqueous humor outflow
Tian B; Geiger B; Epstein DL; Kaufman PLInvestigative Ophthalmology and Visual Science 2000; 41: 619-623
The cytoskeletal involvement in the regulation of aqueous humor outflow is discussed in an important review by Tian, Geiger, Epstein and Kaufman. The trabecular meshwork consists of arrays of collagen beams covered by endothelium-like cells, with extracellular material occupying the spaces between the beams. The layer which probably has maximal flow resistance is the juxtacanalicular or cribriform region that has no collagenous beams but rather several layers immersed in loose ECM. The exact location and nature of the major resistance barrier in the trabecular meshwork is not clear. With age and more so with glaucoma, resistance increases, trabecular meshwork cells decrease, and alterations in the ECM occur. It is suggested that the cells and ECM in the juxtacanalicular region are 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. The cytoskeleton is a complex system of cytoplasmic fibers responsible for numerous cellular processes. It consists of microfilaments, microtubules and intermediate filaments. The microfilaments, 7 nm in diameter, are involved in multiple cellular processes, from cell adhesion and motility to organelle traffic to adhesion-mediated signal transduction. Microtubules comprise 25-nm diameter hollow polar fibers, densely packed near the nucleus, and extending toward the cell periphery. The intermediate filaments are 10 nm in diameter and are perhaps the most skeletal of all cytoskeletal fibers. Several aspects of these three components of the cytoskeleton are discussed. Drugs that affect the cytoskeleton may destroy or stabilize the microfilaments or micro-tubular system. It is important to realize that cytoskeletal filaments are part of an interactive network so that affecting one system may have considerable indirect effects on the others. The authors discuss several drugs that may act on the cytoskeleton: cytochalasins, ethacrynic acid, H-7, a serine-threonine kinase inhibitor, latrunculins, and several protein kinase inhibitors such as staurosporine. As the actomyosin system is present in essentially all cells, drugs acting on the cytoskeleton could have detrimental effects on other anterior segment tissues especially the cornea. It is the authors hope that differences in tissue architecture and physiological milieu between the cornea and the TM may allow the cornea to avoid meaningful change at drug concentrations affecting the TM. This is explained in more detail. They furthermore offer hope that involvement of different molecular targets or mechanisms for different actin-disrupting agents, and a pro-drug, gene therapy or other site-activated approach, could facilitate development of trabecular meshwork selecting 'drugs'.
Dr. B. Tian, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792-3220, USA
Classification:
2.5 Meshwork (Part of: 2 Anatomical structures in glaucoma)
2.6 Aqueous humor dynamics (Part of: 2 Anatomical structures in glaucoma)
