Ciliary body control of organic anions in the aqueous humor of the eye

房水是晶状体周围的透明液体，有助于维持眼睛的形状和光学特性。房水是由睫状体上皮产生的，这是一层细胞，将血流与房水隔室分开。许多有机阴离子，如尿酸，在房水中的浓度低于血浆，这表明它们被主动去除。有机阴离子代表了一类相对广泛的化学物质，包括激素、代谢中间体、药物和环境污染物，它们的过量会破坏正常的生物过程。控制房水中有机阴离子浓度的能力对晶状体特别重要，因为该组织没有血液供应。睫状体上皮与血液供应和房水均有接触，具有调节房水化学成分的独特地位。鉴于有机阴离子相对不渗透于质膜，它们在纤毛体上皮细胞中的有效移动需要膜转运蛋白（有机阴离子转运蛋白）的促进以及细胞能量的输入。本研究的目的是：1)证明睫状体上皮能够在体液-血液方向上运输有机阴离子，并确定其能量需求；2)确定纤毛体上皮中存在哪些有机阴离子转运蛋白及其表达位置；3)通过特异性抑制哪些有机阴离子转运体参与转运过程。该提案中概述的目标支持该研究计划的长期目标，即了解调节房水化学成分的过程，房水是一种对视力至关重要的生理盐水。

Aqueous humor is the transparent fluid surrounding the lens that helps maintain the shape and optical properties of the eye. Aqueous humor is produced by the ciliary body epithelium, a sheet of cells that separates the bloodstream from the aqueous compartment. The concentration of a number of organic anions, such as uric acid, is lower in aqueous humor than plasma, suggesting that they are actively removed. Organic anions represent a relatively broad class of chemicals, including hormones, metabolic intermediates, drugs and environmental contaminants, which in excess can disrupt normal biological processes. The ability to control aqueous humor concentrations of organic anions is of particular importance to the lens, as this tissue has no blood supply. The ciliary body epithelium, being in contact with both the blood supply and aqueous humor, is uniquely positioned to regulate the chemical composition of the aqueous humor. Given that organic anions are relatively impermeable to plasma membranes their efficient movement across ciliary body epithelial cells requires facilitation by membrane transport proteins (organic anion transporters) as well as the input of cellular energy. The aims of this proposal are: 1) to show that the ciliary body epithelium is capable of transporting organic anions in the aqueous humor-to-blood direction and to define the energetic requirements; 2) to determine which organic anion transporters are present in the ciliary body epithelium and where they are expressed; and 3) to identify which of the organic anion transporters are involved in the transport process by specifically inhibiting them. The aims outlined in this proposal support the long-term objective of this research program, which is to understand the processes that regulate the chemical composition of the aqueous humor, a saline vital for vision.