Measurement of Fluid Flow Across the Ocular Ciliary Body

描述(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，通常与眼压升高有关，导致不可逆转的失明。它是全球范围内导致视力丧失的主要原因。鉴于高眼压是导致视网膜损伤的最常见因素，针对青光眼的药物治疗主要集中在增加房水的排出或减少睫状体上皮的产生。然而，对水合物产生的生理机制的清楚理解仍然是难以捉摸的。通过纤毛上皮分泌液体的驱动力是离子传输产生的渗透梯度和流体静压差，它们的相对贡献尚不确定。尽管广泛的研究已经确定了产生渗透梯度所传输的离子，但公布的数据表明，传输速率可能不足以解释液体产生的速率(这意味着超滤的重要性)，并且不存在与所有可用实验数据一致的传输模型。这可能是由于纤毛上皮的复杂性以及所研究物种之间运输元件的差异所致。实际测量液体通过分离的睫状体上皮并不像通常对其他水输送上皮如肾、膀胱和角膜内皮那样进行测量。我们的初步实验表明，我们可以测量这个孤立组织中的液体运输。 因此，本研究的目的是：1)测量具有不同电解质转运特性的牛和兔两种典型组织的纤毛上皮细胞的液体转运；2)研究电解质转运的刺激剂和抑制剂对这两种模型组织液体转运速率的影响；3)研究离子置换和离子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目前对睫状体上皮生理学的了解的空白，并应该提供对离子传输对房水形成的贡献的量化。

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.