Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, AA7103 MCN, 1161 21st Ave. S., Nashville, TN 37232, USA.
Stuart Therapeutics, Inc., 411 SE Osceola St., Suite 203, Stuart, FL 34994, USA.
Int J Mol Sci. 2022 Jun 23;23(13):7004. doi: 10.3390/ijms23137004.
Epithelial cells of multiple types produce and interact with the extracellular matrix to maintain structural integrity and promote healthy function within diverse endogenous tissues. Collagen is a critical component of the matrix, and challenges to collagen's stability in aging, disease, and injury influence survival of adherent epithelial cells. The retinal pigment epithelium (RPE) is important for maintaining proper function of the light-sensitive photoreceptors in the neural retina, in part through synergy with the collagen-rich Bruch's membrane that promotes RPE adherence. Degradation of Bruch's is associated with RPE degeneration, which is implicated early in age-related macular degeneration, a leading cause of irreversible vision loss worldwide. Collagen mimetic peptides (CMPs) effectively repair damage to collagen helices, which are present in all collagens. Our previous work indicates that in doing so, CMPs promote survival and integrity of affected cells and tissues in models of ocular injury and disease, including wounding of corneal epithelial cells. Here, we show that CMPs increase adherence and migration of the ARPE-19 line of human RPE cells challenged by digestion of their collagen substrate. Application of CMPs also reduced both ARPE-19 secretion of pro-inflammatory cytokines (interleukins 6 and 8) and production of reactive oxygen species. Taken together, these results suggest that repairing collagen damaged by aging or other pathogenic processes in the posterior eye could improve RPE adherence and survival and, in doing so, reduce the inflammatory and oxidative stress that perpetuates the cycle of destruction at the root of age-related diseases of the outer retina.
多种类型的上皮细胞产生并相互作用于细胞外基质，以维持结构完整性并促进内源性组织的健康功能。胶原蛋白是基质的关键组成部分，衰老、疾病和损伤时胶原蛋白稳定性的挑战会影响附着上皮细胞的存活。视网膜色素上皮 (RPE) 对于维持光感受器在神经视网膜中的正常功能很重要，部分原因是与富含胶原蛋白的布鲁赫膜协同作用，促进 RPE 附着。布鲁赫膜的降解与 RPE 变性有关，RPE 变性与年龄相关性黄斑变性（全球导致不可逆视力丧失的主要原因）的早期发生有关。胶原蛋白模拟肽 (CMP) 可有效修复所有胶原蛋白中存在的胶原蛋白螺旋损伤。我们之前的工作表明，在这样做的过程中，CMP 促进了眼部损伤和疾病模型中受影响细胞和组织的存活和完整性，包括角膜上皮细胞的创伤。在这里，我们表明 CMP 增加了 ARPE-19 人 RPE 细胞系在其胶原蛋白底物消化时的粘附和迁移。CMP 的应用还减少了 ARPE-19 前炎症细胞因子（白细胞介素 6 和 8）的分泌和活性氧的产生。总之，这些结果表明，修复后眼中由衰老或其他致病过程引起的胶原蛋白损伤可以改善 RPE 的粘附和存活，并由此减少引发外视网膜年龄相关性疾病破坏循环的炎症和氧化应激。
