Measurement of Fluid Flow Across the Ocular Ciliary Body

流过眼部睫状体的液体流量的测量

• 批准号: 6769491
• 负责人: Oscar A Candia
• 金额: $ 19.06万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6769491
• 关键词: animal tissue; electrolytes; epithelium; fluid flow; ion channel blocker; ion transport; iris; laboratory rabbit; measurement; membrane permeability; osmotic pressure; uvea ciliary body

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.

青光眼是一类以退行性视神经病变为特征的疾病，通常与眼压升高（IOP）有关，导致不可逆失明。它是全世界视力丧失的主要原因。鉴于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侧重于增加房水的排出或减少睫状体上皮的产生。然而，对产生水的生理机制的清晰理解仍然是难以捉摸的。液体分泌通过纤毛上皮的驱动力是离子传输产生的渗透梯度和静水压力差，它们的相对贡献尚未确定。尽管广泛的工作已经确定了为产生渗透梯度而被输送的离子，但已发表的数据表明，输送速率可能不足以解释流体产生的速率（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输送模型。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。实际测量液体在离体纤毛上皮上的运动还没有被尝试过，就像通常对其他输水上皮（如肾、膀胱和角膜内皮）所做的那样。我们的初步实验表明，我们可以测量这种分离组织中的液体输送。