Measurement of Fluid Flow Across the Ocular Ciliary Body

描述（由申请人提供）：青光眼是一种以退行性视神经病变为特征的疾病家族，通常与眼内压（IOP）升高相关，导致不可逆性失明。它是全球视力丧失的主要原因。考虑到IOP升高是与视网膜损伤相关的最常见因素，针对青光眼的药物治疗集中在增加房水的排出或减少睫状体上皮的房水产生。然而，对产生水的生理机制的清楚理解仍然是难以捉摸的。跨睫状体上皮的液体分泌的驱动力是由离子转运和流体静压差产生的渗透梯度，其相对贡献尚未确定。虽然大量的工作已经确定了离子传输的渗透梯度的创建，公布的数据表明，传输速率可能不足以占液体生产率（意味着超滤的重要性）和传输模型与所有可用的实验数据不存在。这可能是由于睫状上皮的复杂性，以及运输元素之间的物种研究的变化。还没有尝试过对穿过分离的睫状上皮的流体运动进行实际测量，而通常对其他水运输上皮如肾、膀胱和角膜内皮进行实际测量。我们的初步实验表明，我们可以测量在这个孤立的组织中的液体运输。 因此，本建议的目的是：1）测量液体通过牛和兔的分离睫状上皮的转运，这两种组织表现出不同的电解质转运特性; 2）研究电解质转运的刺激剂和抑制剂对两种模型组织中液体转运速率的影响; 3）研究离子置换和耗竭对液体转运速率的影响。这些相对简单的实验方法将填补一个空白，目前睫状上皮生理学的理解，并应提供一个量化的离子转运水的形成的贡献。

DESCRIPTION (provided by applicant): Glaucoma is a family of diseases characterized by degenerative optic neuropathy, usually related to an elevation in intraocular pressure (IOP), resulting in irreversible blindness. It is a leading cause of vision loss worldwide. Given that elevated IOP is the most common factor associated with retinal damage, pharmacological treatments directed at glaucoma have focused upon increasing the drainage of the aqueous humor or reducing its production by the ciliary epithelium. Yet, a clear understanding of the physiological mechanisms by which the aqueous is produced remains elusive. The driving forces for fluid secretion across the ciliary epithelium are the osmotic gradient created by ionic transport and a hydrostatic pressure difference, with their relative contributions undetermined. Although extensive work has identified the ions that are transported for the creation of the osmotic gradient, published data suggest that the transport rates may be insufficient to account for the rate of fluid production (implying the importance of ultrafiltration) and a transport model consistent with all of the available experimental data does not exist. This may be due to the complexity of the ciliary epithelium as well as variations in transport elements among the species studied. Actual measurements of fluid movement across the isolated ciliary epithelium have not been attempted as commonly done with other water transporting epithelia such as those of the kidney, urinary bladder and corneal endothelium. Our preliminary, experiments show that we can measure fluid transport in this isolated tissue. Therefore, the aims of this proposal are 1) to measure fluid transport across isolated ciliary epithelia from bovine and rabbit, two well characterized tissues manifesting distinct electrolyte transport properties; 2) to study the effects of stimulants and inhibitors of electrolyte transport on the rate of fluid transport in the two model tissues; and 3) to study the effects of ion replacement and depletion on the rate of fluid transport. These relatively simple experimental approaches will fill a void in the present understanding of ciliary epithelial physiology and should provide a quantification of the contribution of ionic transport to aqueous formation.