Modulating intraocular pressure to treat ocular hypotony and glaucoma

 描述(申请人提供)：严重的低眼压[眼内压过低]可导致眼球突出致盲(缩小的、无功能的眼睛)。目前，还没有有效的治疗低眼压的方法。我们最近发现，药物或遗传抑制碳酸氢盐调节的可溶腺苷环化酶(SAC)会提高野生型小鼠和低眼压小鼠的眼压。我们已经在小分子筛查中确定了SAC的抑制剂，并建议将这些SAC抑制剂开发成治疗眼低眼压的一流疗法。我们的小分子筛查还确定了第一个已知的提高SAC活性的药理工具，我们建议测试它们是否为降低眼压治疗青光眼的新治疗策略定义了先导化合物。

 DESCRIPTION (provided by applicant): Severe ocular hypotony [too low intraocular pressure (IOP)] can lead to blindness via Phthisis bulbi (shrunken, non-functional eyes). Currently, there are no effective treatments for hypotony. We recently showed that pharmacologic or genetic inhibition of bicarbonate-regulated soluble adenylyl cyclase (sAC) elevates IOP in wild type mice as well as in a mouse model of ocular hypotony. We have identified inhibitors of sAC in a small molecule screen, and we propose to develop these sAC inhibitors into first-in-class therapeutics for treatment of ocular hypotony. Our small molecule screen also identified the first known pharmacological tools for increasing sAC activity, and we propose to test whether they define lead compounds for a new therapeutic strategy for lowering IOP to treat glaucoma.