GLAUCOMA, LENS AND FLUID SECRETION PHARMACOLOGY

这项研究的广泛目标是增加对分泌物和 眼、脑和内耳中的碳酸氢酶(CA)依赖系统，以及 适用于某些医学问题，特别是青光眼，白内障，增加 颅内压、梅尼耶斯病。生理上的工作就会完成 与适当组织的酶研究同步进行。眼睛：A)搜索 将继续寻找一种有效的无毒碳酸酐酶抑制剂 通过角膜滴注而不是全身治疗青光眼。当前 角膜穿透原理的研究表明这是可行的。研究是 还计划在给药后将离子从血浆转移到水中 噻吗洛尔，与CA抑制剂进行比较。B)将作出重大努力，以 CA在正常晶状体中的作用，我们目前的工作与其异化有关 HCO3-。这一机制似乎在白内障晶状体中失败了。 脑脊液：既是分子探针又是潜在的药物，新的药物(除 CA抑制剂)将减少脑脊液流量仍有待发现。这样的代理人 将寻求，特别注意它们对离子传输的影响。 内淋巴：将寻求有关二氧化碳平衡和形成的基本信息 内淋巴率。我们将测量CA抑制剂对离子和流体的影响 内耳运动。由于这个地区的CA浓度很高， 与其他液体和一些临床“印象”类似，有可能是 这些研究可能导致梅尼尔病的有效治疗。酶学： 将在这些组织上进行CA的基本动力学和抑制研究， 重点是膜结合酶。这些化学数据将会密切地 与生理和药理结果联系在一起，共同形成 为合理的治疗方案奠定基础。

The broad objectives of this research are to increase knowledge of secretory and carbonic anhydrase (CA)-dependent systems in the eye, brain, and inner ear, and apply this to certain medical problems, notably glaucoma, cataract, increased intracranial pressure, & Menieres disease. The physiological work will be done in parallel with enzyme studies on the appropriate tissues. EYE: a) Search will continue for an effective non-toxic carbonic anhydrase inhibitor for treatment of glaucoma by corneal instillation rather than systemically. Current work on principles of corneal penetration show this to be feasible. Studies are also planned on ion-transport from plasma to aqueous following administratin of timolol, to compare with CA inhibitors. b) Major effort will be given to the role of CA in normal lens, which our current works links to dissimilation of HCO3-. It appears likely that this mechanism fails in cataractous lens. BRAIN-CSF: Both as molecular probes and potential drugs, new agents (other than CA inhibitors) remain to be discovered that will reduce CSF flow. Such agents will be sought, with particular attention to their influence on ion transport. ENDOLYMPH: Basic information will be sought on CO2 equilibria and formation rate of endolymph. We shall measure effects of CA inhibitors on ion and fluid movement in inner ear. Because of the high concentration of CA in this locale, analogy to the other fluids and some clinical "impressions", it is possible that these studies may lead to effective treatment of Menieres disease. ENZYMOLOGY: Basic kinetics and inhibition studies of CA will be done on these tissues, with emphasis on the membrane-bound enzyme. These chemical data will be intimately linked to the physiological and pharmacological results, and together form the basis for rational treatment programs.