International Ocular Surface Research Center, Institute of Ophthalmology, Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Pathology, Jinan University Medical School, Guangzhou, China.
Exp Eye Res. 2022 Jul;220:109111. doi: 10.1016/j.exer.2022.109111. Epub 2022 May 13.
Thyroid hormones have a critical role in maintaining metabolic and physiological homeostasis. However, understanding of the possible effects of thyroid dysfunction on corneal homeostasis and the wound healing process is quite limited. To explore the influence of hypothyroidism on corneal homeostasis and the post-wound repair processes of the murine cornea.
A hypothyroidism model was established by total thyroidectomy (TThy) in C57BL/6J mice. On day 10 after TThy, hypothyroidism was confirmed via thyronine (T3 and T4) and thyroid-stimulating hormone serum levels. We further assessed changes in corneal thickness, corneal sensitivity, sub-basal nerve density, and the corneal expression of thyroid hormone receptors. A corneal epithelial abrasion model was established via mechanical removal of a central epithelium 2 mm in diameter. Wound closure and recruitment of inflammatory cells (neutrophils and γδ T-cells) were evaluated. RNA-sequencing and gene set enrichment analysis were performed in injured corneas after abrasion. The effect of local T3 administration on corneal wound healing in thyroidectomized mice was also observed.
Compared with sham-operated control mice, the TThy-treated mice showed the following: (1) a significant decrease in corneal epithelial thickness, sensitivity to external stimuli, and sub-basal nerve density, as well as an alteration in thyroid hormone receptor expression in the steady state; (2) delayed corneal wound repair and enhanced inflammatory response after corneal abrasion; (3) down-regulation of actin-skeleton and DNA replication pathways and up-regulation of inflammation-associated pathways in abraded corneas; and (4) significant restoration of delayed corneal wound repair and inhibition of excessive inflammation following topical T3 administration.
We conclude that deficient thyroid hormone secretion significantly affects corneal homeostasis and post-wound repair processes. Topical T3 administration might have a potential reversal effect on delayed corneal wound repair among hypothyroid individuals.
甲状腺激素在维持代谢和生理稳态方面起着关键作用。然而，对于甲状腺功能障碍对角膜稳态和伤口愈合过程的可能影响，人们的了解相当有限。本研究旨在探讨甲状腺功能减退症对角膜稳态和小鼠角膜伤口修复过程的影响。
通过对 C57BL/6J 小鼠进行甲状腺全切除术（TThy）建立甲状腺功能减退症模型。在 TThy 后第 10 天，通过甲状腺素（T3 和 T4）和促甲状腺激素血清水平确认甲状腺功能减退症。我们进一步评估了角膜厚度、角膜敏感度、基底下神经密度以及角膜甲状腺激素受体表达的变化。通过机械去除直径 2mm 的中央上皮建立角膜上皮磨损模型。评估伤口闭合和炎症细胞（中性粒细胞和 γδ T 细胞）的募集情况。对磨损后的角膜进行 RNA 测序和基因集富集分析。还观察了局部 T3 给药对甲状腺切除小鼠角膜伤口愈合的影响。
与假手术对照小鼠相比，TThy 处理的小鼠表现出以下特征：（1）角膜上皮厚度、对外界刺激的敏感性和基底下神经密度显著降低，以及甲状腺激素受体表达在稳态时发生改变；（2）角膜磨损后角膜伤口修复延迟和炎症反应增强；（3）磨损的角膜中肌动蛋白骨架和 DNA 复制途径下调以及炎症相关途径上调；（4）局部 T3 给药后明显恢复了角膜伤口修复的延迟，并抑制了炎症的过度发生。
我们得出结论，甲状腺激素分泌不足会显著影响角膜稳态和伤口愈合过程。局部 T3 给药可能对甲状腺功能减退个体的角膜伤口修复延迟具有潜在的逆转作用。
