Retinal Physiology in Experimental Glaucoma

描述(申请人提供)：最大限度地保护视觉功能是青光眼研究的主要目标。只要视力正常，患者就不会关心他或她的眼压或视盘地形图。因此，青光眼对视网膜神经节细胞的生理特性的影响几乎一无所知，这似乎令人惊讶。视网膜神经节细胞正是为大脑提供视觉输入的细胞，也是疾病的靶点。该研究项目的目的是填补我们对青光眼认识上的这一重要空白。该研究项目建议通过在体内记录压力诱导青光眼大鼠模型中单个视束纤维的视觉诱发活动来实现这一目标，并直接测试慢性高血压眼视网膜神经节细胞在细胞死亡之前功能特征发生变化的假设。其具体目的是定量描述：1)正常大鼠神经节细胞的时空反应特性；2)慢性高眼压大鼠神经节细胞的时空反应特性。 这项研究的一个可能结果是，青光眼对神经节细胞生理没有不良影响。对于所有密集的目的，细胞的行为都是正常的，直到它们收到死亡的凋亡信号。这将降低使用非侵入性方法检测青光眼的前景，因为这些方法检测疾病的细胞总是必须死亡。另一种可能的结果是，高眼压改变了存活的神经节细胞的平均刺激率、感受野大小或其他反应特性。生理效应可能仅限于某些类型的神经节细胞，也可能被所有类型的神经节细胞所共享。这一结果不仅将为青光眼的早期检测描绘出一幅更有希望的图景，还将建议进行最能揭示知觉缺陷的视力测试，从而有助于加快抗击这种令人衰弱的疾病的进展。 公共卫生：青光眼是一种眼病，它会杀死为大脑提供视觉输入的细胞。这项研究的目的是确定青光眼如何影响这些细胞的神经信息，而这些细胞仍然活着。这些信息可以用来设计新的视力测试，以便在早期阶段发现疾病。

DESCRIPTION (provided by applicant): Maximum preservation of visual function is the main goal of glaucoma research. A patient cares little about his or her intraocular pressure or optic disc topography so long as their sight is normal. It may thus seem surprising that virtually nothing in known about the effect of glaucoma on the physiological properties of retinal ganglion cells, the very cells that provide the brain with visual input and that are targeted by the disease. The objective of the research project in to fill this important gap in our understanding of glaucoma. The research project proposes to do so by recording in vivo the visually-evoked activity of single optic tract fibers in the rat model of pressure-induced glaucoma and putting directly to test the hypothesis that the functional characteristics of retinal ganglion cells change in chronically hypertensive eyes before the cells die. The specific aims are to quantitatively characterize: 1) the spatiotemporal response properties of ganglion cells in normal rats and 2) the spatiotemporal response properties of ganglion cells in rats with chronic ocular hypertension. One possible outcome of the research is that glaucoma has no ill effects on ganglion cell physiology. For all intensive purposes the cells behave normally up until the moment they receive the apoptotic signal to die. This would dampen the prospects of using non-invasive methods, like vision tests and electroretinograms, for glaucoma detection since cells would invariably have to die for these methods to detect the disease. The other possible outcome is that ocular hypertension alters the mean spike rate, receptive field size, or other response properties of surviving ganglion cells. The physiological effects might be confined to certain types of ganglion cell or shared by them all. This outcome would not only paint a more promising picture for early glaucoma detection but also suggest the kinds of vision test that would best reveal perceptual deficits, which would thereby help speed progress in the fight against the debilitating disease. Public Health: Glaucoma is an eye disease that kills the cells that provide visual input to the brain. The aim of this research is determine how glaucoma affects the neural messages of these cells while the cells are still alive. This information could be used to design novel vision tests that detect the disease at an early stage.