Hypothyroidism affects corneal homeostasis and wound healing in mice

Yijia Huang; Ting Fu; Xinwei Jiao; Sijing Liu; Yunxia Xue; Jun Liu; Zhijie Li

doi:10.1016/j.exer.2022.109111

Hypothyroidism affects corneal homeostasis and wound healing in mice

Exp Eye Res. 2022 Jul:220:109111. doi: 10.1016/j.exer.2022.109111. Epub 2022 May 13.

Authors

Yijia Huang¹, Ting Fu¹, Xinwei Jiao², Sijing Liu¹, Yunxia Xue³, Jun Liu³, Zhijie Li⁴

Affiliations

¹ 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.
² Department of Pathology, Jinan University Medical School, Guangzhou, China.
³ International Ocular Surface Research Center, Institute of Ophthalmology, Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China.
⁴ 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. Electronic address: tzhijieli@jnu.edu.cn.

PMID: 35569517
DOI: 10.1016/j.exer.2022.109111

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cornea; Inflammation; Thyroid dysfunction; Wound healing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cornea / metabolism
Corneal Injuries* / metabolism
Epithelium, Corneal* / metabolism
Homeostasis
Hypothyroidism* / metabolism
Inflammation / metabolism
Mice
Mice, Inbred C57BL
Wound Healing / physiology