Reversible Ganglion Cell Dysfunction in Glaucoma

描述（由申请人提供）：青光眼视神经病变的视力丧失是由于视网膜神经节细胞（RGC）的死亡。我们的长期目标是验证这样的假设，即在青光眼视神经病变的早期阶段，RGC功能障碍先于其死亡，如果这种功能障碍首先被发现并加以治疗，视力可能会得到挽救。我们的直接目标是了解青光眼进展中RGC的潜在可逆功能变化和不可逆结构变化之间的关系。我们的合作研究团队结合了青光眼、视觉电生理学、生物物理学和视网膜成像方面的专业知识，在一个独特的临床研究环境中工作，该环境中有大量疑似青光眼的患者，其中包括高比例的非洲裔美国人和西班牙裔人。我们将使用我们开发的非侵入性技术来评估RGC的功能和结构-包括模式视网膜电图（PERG）来测量RGC潜在的可逆功能变化，以及光学相干断层扫描（OCT）来测量RGC及其轴突的不可逆结构变化-在这些患者的选定组中。我们还将使用非侵入性的范例-吸盘增加眼内压（IOP）和局部治疗降低IOP -来确定PERG异常是否依赖于IOP。具体目的是：1)识别和表征青光眼疑似患者的PERG异常；2)了解PERG丢失与OCT丢失之间的关系；3)了解PERG异常与诱导IOP变化之间的关系。这种结合的创新方法将更好地理解青光眼神经病变进展的病理生理机制，可能为青光眼的治疗或预防提供理论依据，并将开发一种基于RGC功能监测治疗效果的方法。

DESCRIPTION (provided by applicant): Loss of sight in glaucomatous optic neuropathy is due to the death of retinal ganglion cells (RGC). Our long-term goal is to test the hypothesis that dysfunction of RGC precedes their death in early stages of glaucomatous optic neuropathy, and that vision may be spared if this dysfunction is first detected and then treated. Our immediate goal is to understand the relationships between potentially reversible functional changes and irreversible structural changes of RGC in the progression of glaucoma. Our collaborative research team combines expertise in glaucoma, visual electrophysiology, biophysics, and retinal imaging, working in a unique clinical-research setting that has a large number of patients with suspicion of glaucoma including high rates of individuals of African American and Hispanic descent. We will use non-invasive techniques that we developed to evaluate RGC function and structure - including the pattern electroretinogram (PERG) to measure potentially reversible functional changes of RGC, and Optical Coherence Tomography (OCT) to measure irreversible structural changes of RGC and their axons - in selected groups of these patients. We will also use non-invasive paradigms - suction cup to increase the intraocular pressure (IOP) and topical treatment to lower IOP - to establish whether PERG abnormalities depend on IOP. The specific aims are: 1) to identify and characterize PERG abnormalities in glaucoma suspects, 2) to understand the relationship between PERG losses and OCT losses, and 3) to understand the relationship between PERG abnormalities and induced changes in IOP. This combined, innovative approach will yield a better understanding of the pathophysiological mechanisms in the progression of glaucomatous neuropathy, may provide a rationale for treatment or prevention of glaucoma, and will develop a method to monitor the efficacy of treatment based on RGC function.