CORNEAL NEUROBIOLOGY

拟议的研究将扩展该实验室先前的发现。 以扩大我们对新陈代谢和生理的了解 角膜的神经支配与角膜的关系 上皮组织。以前开发的定量、解剖学和 评估结构和功能方面的生理学方法 感觉神经支配将被应用于理解潜在的 众所周知但知之甚少的角膜减少的原因 由于戴隐形眼镜和糖尿病引起的敏感性。角膜 将在兔身上研究戴隐形眼镜后的敏感度变化。 这项工作的目的将是确定隐形眼镜如何影响 角膜中的感觉传递。注射链脲佐菌素致糖尿病大鼠 链脲佐菌素将以不同的间隔用光和 用电子显微镜确定神经退行性变的过程。 对糖尿病患者的心理物理研究将关联到 角膜敏感度与其他神经变化相结合以确定 角膜可以提供一个独特的窗口，了解早期感觉神经的变化 糖尿病患者。其他研究将决定放射性标记的命运 轴浆物质从三叉神经节输送到三叉神经节 角膜上皮，以及这些材料可能成为的途径 可供上皮细胞使用。神经再生后 将进行穿透性角膜移植检查，以确定 恢复正常的角膜神经功能。将确定是否 上皮细胞胆碱摄取的高亲和力和低亲和力系统均存在 细胞；以及特定的去神经对角膜的影响和变化 在上皮细胞有丝分裂活动中，如在伤口愈合中，对胆碱 将研究摄取系统。电生理研究将允许 角膜感觉的解剖学与生理学相关性研究 通过三叉神经节细胞内记录受体， 然后注射轴浆运输的示踪剂。另外， 以伤口为导向的侧芽的感官能力将是 对机械、热和化学刺激的反应进行评估。它 可能是在响应参数中看到的更改类型 特征将使我们更深入地了解 产生与角膜损伤相关的异常感觉。 来自这些研究的信息可能会导致新的 促进角膜伤口愈合的治疗方法。

The proposed studies will extend the previous findings of this laboratory to expand our understanding of the metabolic and physiological relationships between the innervation of the cornea and the corneal epithelium. Previously developed quantitative, anatomical, and physiological methods for assessing structural and functional aspects of the sensory innervation will be applied to understanding the underlying causes of the well-known, but poorly understood decreased corneal sensitivity attributed to contact lens wear and to diabetes. Corneal sensitivity changes after contact lens wear will be studied in the rabbit. The object of this work will be to determine how contact lenses affect sensory transmission in the cornea. Rats made diabetic by injection of streptozotocin will be examined at various intervals by means of light and electron microscopy to determine the course of neural degeneration. Psychophysical studies of diabetic patients will correlate changes in corneal sensitivity with other neurological changes to determine if the cornea could provide a unique window into early sensory nerve changes in diabetics. Other studies will determine the fate of radiolabeled substances axoplasmically transported from the trigeminal ganglion to the corneal epithelium, and the routes by which these materials could become available to the epithelial cells. Nerve regeneration following penetrating keratoplasty will be examined to identify the barriers to restoration of the normal corneal neurology. It will be determined whether both high- and low-affinity systems exist for choline uptake in epithelial cells; also, the effects of specific denervation of the cornea and changes in epithelial mitotic activity, such as in wound healing, on the choline uptake system will be studied. Electrophysiological studies will permit the correlation of the anatomy and physiology of the corneal sensory receptors by intracellular recording from trigeminal ganglion cells, followed by the injection of an axoplasmically-transported tracer. Also, the sensory capabilities of wound-oriented collateral sprouts will be assessed in response to mechanical, thermal, and chemical stimulation. It may be that the types of changes seen in the parameters of the response characteristics will yield some insight into the mechanisms involved in the production of the abnormal sensations associated with corneal injury. Information from these studies could lead to the development of new therapeutic methods for accelerating corneal wound healing.