Patients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model of cEDS (). We found that collagen V reexpression in this model is upregulated during corneal tissue repair and that wound healing is delayed, impaired, and results in large atrophic corneal scars. We noted that in a matrix with a 50 % content of collagen V, activation of latent Transforming Growth Factor (TGF) β is dysregulated. Corneal myofibroblasts with a haploinsufficiency of collagen V failed to mechanically activate latent TGF β. Second harmonic imaging microscopy showed a disorganized, undulated, and denser collagen matrix in our model that suggested alterations in the extracellular matrix structure and function. We hypothesize that a regenerated collagen matrix with only 50 % content of collagen V is not resistant enough mechanically to allow adequate activation of latent TGF β by fibroblasts and myofibroblasts.

中文翻译：

---

经典 Ehlers-Danlos 模型中角膜损伤后功能失调的潜在转化生长因子 β 激活


患有经典埃勒斯丹洛斯综合征 (cEDS) 的患者伤口愈合受损，受伤后形成萎缩性疤痕，难以通过手术闭合。 COL5A1 的单倍体不足会导致整个身体发生系统性形态和功能改变。我们在 cEDS 小鼠模型中研究了损害角膜撕裂伤（全层损伤）伤口愈合的机制 ()。我们发现，该模型中胶原蛋白 V 的再表达在角膜组织修复过程中上调，并且伤口愈合延迟、受损，并导致大面积萎缩性角膜疤痕。我们注意到，在胶原蛋白 V 含量为 50% 的基质中，潜在转化生长因子 (TGF) β 的激活失调。胶原蛋白 V 单倍体不足的角膜肌成纤维细胞无法机械激活潜在的 TGF β。二次谐波成像显微镜显示我们的模型中存在杂乱、起伏且致密​​的胶原基质，这表明细胞外基质结构和功能发生了变化。我们假设，仅含 50% 胶原蛋白 V 的再生胶原蛋白基质的机械抵抗力不足以允许成纤维细胞和肌成纤维细胞充分激活潜在的 TGF β。