Baratta Robert O, Del Buono Brian J, Schlumpf Eric, Ceresa Brian P, Calkins David J
Stuart Therapeutics, Stuart, FL, United States.
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY, United States.
Front Pharmacol. 2021 Aug 16;12:705623. doi: 10.3389/fphar.2021.705623. eCollection 2021.
The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barrier to environmental, microbial, and other insults. Renewal and migration of basal epithelial cells from the limbus involve critical interactions between secreted basement membranes, composed primarily of type IV collagen, and underlying Bowman's and stromal layers, which contain primarily type I collagen. This process is challenged in many diseases and conditions that insult the ocular surface and damage underlying collagen. We investigated the capacity of a collagen mimetic peptide (CMP), representing a fraction of a single strand of the damaged triple helix human type I collagen, to promote epithelial healing following an acute corneal wound. , the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an mouse model, topical application of a CMP-containing formulation following a 360° lamellar keratectomy targeting the corneal epithelial layer accelerated wound closure during a 24 h period, compared to vehicle. We found that the CMP increased adherence of the basal epithelium to the underlying substrate and enhanced density of epithelial cells, while reducing variability in the regenerating layer. These results suggest that CMPs may represent a novel therapeutic to heal corneal tissue by repairing underlying collagen in conditions that damage the ocular surface.
眼睛的角膜由于持续暴露于眼外环境而有受伤风险。角膜是一种高度胶原化的结构,包含分布在多层中的几种不同类型的胶原。最外层含有未角化的上皮细胞,它们作为抵御环境、微生物和其他侵害的屏障。来自角膜缘的基底上皮细胞的更新和迁移涉及主要由IV型胶原组成的分泌性基底膜与下方主要含有I型胶原的Bowman层和基质层之间的关键相互作用。在许多损害眼表并破坏其下方胶原的疾病和病症中,这一过程受到挑战。我们研究了一种胶原模拟肽(CMP)促进急性角膜伤口上皮愈合的能力,该肽代表受损三螺旋人I型胶原单链的一部分。这种胶原模拟肽促进了酶消化损伤的胶原的重新排列。在小鼠模型中,与赋形剂相比,在针对角膜上皮层的360°板层角膜切除术后局部应用含CMP的制剂在24小时内加速了伤口闭合。我们发现CMP增加了基底上皮与下方基质的粘附,并提高了上皮细胞的密度,同时降低了再生层的变异性。这些结果表明,在损害眼表的病症中,CMP可能代表一种通过修复下方胶原治愈角膜组织的新型疗法。