Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration.
Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration.
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DOI：
10.3389/fphar.2021.705623
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发表时间：
2021
影响因子：
5.6
通讯作者：
Calkins DJ
中科院分区：
文献类型：
--
作者：
Baratta RO;Del Buono BJ;Schlumpf E;Ceresa BP;Calkins DJ
眼睛的角膜由于持续暴露于眼外环境而处于损伤的风险中。角膜是一种高度胶原化的结构，包含分布在多个层中的几种不同类型。最前面的层包含非角质化上皮细胞，其充当对环境、微生物和其他损害的屏障。基底上皮细胞从利姆布斯的更新和迁移涉及主要由IV型胶原组成的分泌的基底膜与主要含有I型胶原的下面的Bowman和基质层之间的关键相互作用。这一过程在许多损害眼表和损害底层胶原蛋白的疾病和病症中受到挑战。我们研究了胶原蛋白模拟肽（CMP）的能力，代表一个单链的受损的三螺旋人类I型胶原蛋白的一部分，以促进上皮愈合后，急性角膜伤口。在体外实验中，胶原模拟肽促进酶消化损伤的胶原重新排列。在体内小鼠模型中，与载体相比，在靶向角膜上皮层的360°板层角膜切除术后局部施用含CMP的制剂在24小时期间加速伤口闭合。我们发现CMP增加了基底上皮对下层基质的粘附，并增强了上皮细胞的密度，同时降低了再生层的变异性。这些结果表明，CMP可能代表一种新的治疗方法，通过修复眼表损伤条件下的底层胶原来愈合角膜组织。
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. In vitro, the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an in vivo 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.
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