Ferrer Elisa
Laboratory of Neurophysiology, Department of Physiological Sciences, Institute of Biomedical Investigations August Pi i Sunyer, School of Medicine, University of Barcelona, Spain.
Drug News Perspect. 2006 Apr;19(3):151-8. doi: 10.1358/dnp.2006.19.3.985929.
Glaucoma, a group of optic neuropathies, is one of the leading causes of irreversible blindness in the world. It is characterized by degeneration of the optic nerve and progressive visual field loss, often associated with elevated intraocular pressure (IOP). In primary open-angle glaucoma, the most common form of the disease, IOP occurs as a result of abnormally increased resistance to drainage of aqueous humor through the conventional outflow system, which comprises the trabecular meshwork and the Schlemm's canal. The pharmacological treatment of glaucoma has been classically aimed at lowering elevated IOP, either decreasing the production of aqueous humor or improving its outflow. Increasing knowledge of trabecular meshwork physiology shows that this tissue has unique morphologic and functional properties involved in the regulation of aqueous humor outflow. Although trabecular meshwork physiology is yet to be fully revealed, ion channels involved in cell contractility or cell volume regulation, or those capable of responding to high pressure, have been described and may be considered promising pharmacological targets for the treatment of glaucoma. The cytoskeleton architecture of the trabecular meshwork cell is thought to be an important regulator of aqueous humor outflow. Gene technology directed at discovering genes linked to the development of glaucoma or to those upregulated in response to elevated IOP is challenging research but provides an insight into future gene therapy. New tools to study trabecular meshwork physiology have recently been developed, including the use of lentivirus for gene delivery or fusion proteins with a protein transduction domain. These vectors are targeted specifically to the trabecular meshwork and are powerful techniques with broad applications for future gene therapy or as new forms of drug delivery.
青光眼是一组视神经病变，是全球不可逆性失明的主要原因之一。其特征是视神经变性和进行性视野缺损，常伴有眼压升高（IOP）。在原发性开角型青光眼（该病最常见的形式）中，眼压升高是由于通过由小梁网和施莱姆管组成的传统流出系统引流房水的阻力异常增加所致。青光眼的药物治疗传统上旨在降低升高的眼压，要么减少房水生成，要么改善房水流出。对小梁网生理学认识的不断增加表明，该组织具有参与房水流出调节的独特形态和功能特性。尽管小梁网生理学尚未完全揭示，但已描述了参与细胞收缩性或细胞体积调节的离子通道，或那些能够对高压作出反应的离子通道，它们可能被视为治疗青光眼有前景的药物靶点。小梁网细胞的细胞骨架结构被认为是房水流出的重要调节因子。旨在发现与青光眼发展相关基因或对眼压升高作出反应而上调的基因的基因技术是一项具有挑战性的研究，但为未来的基因治疗提供了见解。最近开发了研究小梁网生理学的新工具，包括使用慢病毒进行基因传递或与蛋白质转导结构域的融合蛋白。这些载体专门靶向小梁网，是未来基因治疗或新型药物递送具有广泛应用的强大技术。
