ELECTROPHYSIOLOGY & BIOPHYSICS OF CORNEAL WOUND HEALING

受伤后，无论是创伤、手术还是 感染，角膜利用各种细胞机制来修复 它本身。这些事件包括再上皮化，胶原修复通过 角质形成细胞和内皮细胞与区域内皮细胞的再增殖 在那里它已经被剥离了。这一过程非常有效，而且 通常导致角膜的完全愈合，而没有相关的视力 减损。不幸的是，伤口修复过程也可能导致 间质水肿、疤痕形成、溃疡或屈光不正 手术程序和穿透性角膜移植，不可预测和 可能是波动的屈光不正。为了更好地了解和 可能是为了更好地控制伤口愈合过程，了解 角膜创伤愈合的基本细胞机制是必不可少的。 细胞膜中的离子通道已被证明是重要的 细胞激活、有丝分裂和细胞等事件中的介体 增殖、迁移、体积调节、分泌和对 增长因素。因为所有这些事件都涉及到响应 角膜创面愈合过程中角膜基质细胞和内皮细胞的变化 过程中，对离子通道和离子通道之间相互作用的理解 这些事件至关重要。初步数据显示，手术受伤的人 兔角膜内皮细胞具有不同于 在未受伤的对照眼里。有趣的是，这些洋流 与在培养的内皮细胞中看到的相似。在角质形成细胞中， 初步数据显示，胎牛血清刺激，一种已知 这种细胞类型的“激活剂”会导致波幅的快速增加 膜电流的变化。这一效应似乎与这两种情况有关 一种新的通道类型以及电压敏感钠的激活 频道。当8-溴-cAMP 加到浴缸里了。这笔赠款的具体目的是为了 具体涉及生物物理性质和生理相关性 这些初步发现中的许多。 初步研究将利用全细胞和单通道膜片钳 表征和确定损伤机制的技术 内皮细胞和角质形成细胞离子通道活性的变化。此外, 这些变化的生理和药理学意义将 使用体内伤口愈合研究和体外研究进行检查 血流灌注研究。

Following injury, whether it be the result of trauma, surgery, or infection, the cornea utilizes a variety of cellular mechanisms to repair itself. These events include reepithelialization, collagen repair via keratocytes and endothelium, and repopulation of the endothelium in areas in which it has been denuded. This process can be quite effective and often leads to complete healing of the cornea with no associated visual impairment. Unfortunately, the wound repair process can also result in stromal edema, scarring, ulceration, or in the case of refractive surgical procedures and penetrating keratoplasty, unpredictable and possibly fluctuating refractive errors. To better understand and possibly to better control the wound healing process, an understanding of the basic cellular mechanisms of corneal wound healing is essential. Ion channels in cellular membranes have been shown to be important mediators in events such as cell activation, mitogenesis and cell proliferation, migration, volume regulation, secretion, and responses to growth factors. Because all of these events are involved in the response of keratocytes and endothelial cells during the corneal wound healing process, the understanding of the interaction between ion channels and these events is crucial. Preliminary data shows that surgically wounded rabbit corneal endothelial cells have different ionic currents than those in the non-wounded control eye. Interestingly, these currents are similar to those seen in cultured endothelial cells. In keratocytes, preliminary data shows that fetal bovine serum stimulation, a known "activator" of this cell type, causes a rapid increase in the amplitude of the membrane currents. This effect appears to be associated with both activation of a new channel type as well as the voltage sensitive Na+ channel. A similar current activation is observed when 8-bromo-cAMP is added to the bath. The specific aims of this grant are designed to specifically address the biophysical nature and physiological relevance of many of these preliminary findings. Initial studies will utilize whole cell and single channel patch clamp techniques to characterize and determine the mechanisms of injury induced changes in endothelium and keratocyte ion channel activity. In addition, the physiological and pharmacological significance of these changes will be examined using in-vivo wound healing studies as well as in-vitro perfusion studies.