Significance of Corneal Cell Invasion by Bacteria

角膜溃疡是导致角膜失明的最常见原因之一。隐形眼镜佩戴者 在那些年发病率约为1/4000的高危人群中，如果将软(水凝胶)镜片戴在 以日常磨损为基础，在延长磨损期间增加到~1/500。目前有9500多万 全球隐形眼镜佩戴者仅在美国就有3500万人。铜绿假单胞菌最多 通常分离出的致病菌，最有可能导致永久性视力丧失，因为它 攻击性很强，很难治疗。我们的长期目标是了解 戴隐形眼镜易患角膜感染，以期开发新的治疗策略 治疗干预和预防。 通常情况下，角膜上皮提供了一种有效的屏障，防止细菌渗透。这个 我们提出的发病机制模型是，隐形眼镜配戴干扰了眼部的天然防御。 表面，从而使细菌能够在没有明显全厚度的情况下穿透角膜上皮 上皮损伤。初步数据显示，泪液中存在表面活性蛋白D(SP-D)， 这种物质是细菌侵袭角膜上皮的关键天然抑制物 细胞，角膜炎发病机制中的重要一步。因此，这项提案提出了一项审查计划 眼表SP-D及其限制铜绿假单胞菌感染性的活性 假设在正常情况下，铜绿假单胞菌不会侵袭角膜上皮细胞。 因为眼表SP-D结合了细菌脂多糖外核上的葡萄糖残基，所以使用 对于侵袭性，隐形眼镜配戴通过减少铜绿假单胞菌对角膜上皮的穿透 SP-D在眼表的表达。三个具体目的是：1)阐明SP-D的作用机制 抑制铜绿假单胞菌对角膜上皮细胞的侵袭，2)检查是否减少了隐形眼镜的佩戴 眼表SP-D在正常、损伤和细菌感染的角膜中的表达，以及3)确定 隐形眼镜佩戴/SP-D耗尽可使细菌在体内穿透角膜上皮。

Corneal ulceration is one of the most common causes of corneal blindness. Contact lens wearers are among those at greatest risk with an annual incidence of ~1/4000 when soft (hydrogel) lenses are worn on a daily wear basis, increasing to ~ 1/500 during extended wear. There are currently more than 95 million contact lens wearers worldwide, -35 million in the US alone. Pseudomonas aeruginosa is the most commonly isolated causative bacterial pathogen, and the most likely to cause permanent vision loss because it is highly aggressive and difficult to treat. Our long-term goal is to understand the mechanisms by which contact lens wear predisposes to corneal infection, with a view towards developing new strategies for therapeutic intervention and prophylaxis. Ordinarily, the corneal epithelium provides an effective barrier against bacterial penetration. The pathogenesis model that we propose is that contact lens wear interferes with innate defenses at the ocular surface, thereby enabling bacteria to penetrate the corneal epithelium in the absence of overt full-thickness epithelial injury. Preliminary data show that surfactant protein D (SP-D) is present in tear fluid and the corneal epithelium, and that this substance is a key natural inhibitor of bacterial invasion of corneal epithelial cells, an important step in the pathogenesis of keratitis. This proposal, therefore, advances a plan to examine ocular surface SP-D and its activities in limiting the infectivity of P. aeruginosa. The hypothesis is that under normal conditions P. aeruginosa does not invade corneal epithelial cells because ocular surface SP-D binds glucose residues on bacterial lipopolysaccharide outer core that are used for invasion, and that contact lens wear promotes P. aeruginosa penetration of corneal epithelium by reducing ocular surface expression of SP-D. The three specific aims are; 1) to elucidate the mechanism by which SP-D inhibits P. aeruginosa invasion of corneal epithelial cells, 2) to examine whether contact lens wear reduces ocular surface SP-D expression in normal, wounded and bacterial challenged corneas, and 3) to determine if contact lens wear/SP-D depletion enables bacterial penetration through the corneal epithelium in vivo.