Reversible Ganglion Cell Dysfunction in Glaucoma

描述：青光眼性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。我们的长期目标是挽救功能障碍的RGC，以防止青光眼早期阶段的细胞死亡。本研究的目的是确定RGC功能障碍与眼内压（IOP）诱导变化之间的关系，以及RGC功能障碍与死亡之间的关系。我们的中心假设是RGC功能障碍先于RGC死亡，并且可以通过降低IOP来逆转。我们的研究团队包括青光眼、视觉电生理学、视网膜成像和生物物理学方面的专家。我们的临床环境中有一个独特的大量青光眼患者和老年受试者的青光眼风险增加，由于非洲裔美国人和西班牙裔。具体目的是1）检验RGC功能障碍由IOP引起并且可以通过降低IOP逆转的假设，和2）检验在青光眼进展中的任何给定时间RGC功能障碍大于RGC损失的假设。 由RGC损失和活性RGC功能障碍引起的功能损失将用图形视网膜电图（PERG）测量，RGC的解剖损失将用光学相干断层扫描（OCT 3）测量。这两种措施进行了优化，以探测同等数量的神经元具有可比的灵敏度。初步结果支持了假设，初步结果表明，降低IOP的治疗改善了PERG缺陷，暂时性IOP增加加剧了PERG缺陷，并且PERG损失相对大于OCT损失。这种结合，创新的方法将产生一个更好的理解的病理生理机制参与青光眼的进展。预计这项研究将为青光眼的早期治疗或预防提供理论依据，并将开发一种基于PERG改善量监测治疗效果的方法。由于青光眼失明随着寿命的增加而稳步增长，这些结果预计将对减轻我国的医疗保健负担产生很大的潜在影响。

DESCRIPTION: Loss of sight in glaucomatous optic neuropathy is due to the death of retinal ganglion cells (RGCs). Our long-term goal is to rescue dysfunctioning RGCs to prevent cell death in the early stages of glaucoma. The objective of this study is to define the relationship between RGC dysfunction and induced changes of the intraocular pressure (lOP), and that between RGC dysfunction and death over time. Our central hypothesis is that RGC dysfunction precedes RGC death and can be reversed by lowering the lOP. Our research team includes experts in glaucoma, visual electrophysiology, retinal imaging, and biophysics. Our clinical setting has a uniquely large population of glaucoma patients and older subjects at increased risk of glaucoma due to African-American and Hispanic ethnicity. The specific aims are 1) to test the hypothesis that RGC dysfunction is caused by lOP and can be reversed by lowering lOP, and 2) to test the hypothesis that RGC dysfunction is larger than RGC loss at any given time in the progression of glaucoma. Functional losses resulting from both RGC loss and dysfunction of viable RGCs will be measured with the pattern electroretinogram (PERG), and anatomic loss of RGCs will be measured with Optical Coherence Tomography (OCT3). Both measures are optimized to probe an equivalent number of neurons with comparable sensitivity. Hypotheses are supported by preliminary results showing that PERG deficits are improved by lOP-lowering treatments, and exacerbated by temporary lOP increases, and that PERG losses are relatively larger than OCT losses. This combined, innovative approach will yield a better understanding of the pathophysiological mechanisms involved in the progression of glaucoma. It is expected that this research will provide a rationale for the early treatment or prevention of glaucoma, and will develop a method to monitor the efficacy of treatment based on the amount of PERG improvement. Since blindness from glaucoma is steadily growing with increasing longevity, these results are expected to have a high potential impact on alleviating the health care burden in our country.