Wound Healing of the Corneal Epithelium: a Review

Overview

Journal Asian Biomed (Res Rev News)

Date 2023 Aug 8

PMID 37551323

Authors

Norzana Abd Ghafar

Nahdia Afiifah Abdul Jalil

Taty Anna Kamarudin

Affiliations

Soon will be listed here.

Abstract

The corneal epithelium (CE) forms the outermost layer of the cornea. Despite its thickness of only 50 μm, the CE plays a key role as an initial barrier against any insults to the eye and contributes to the light refraction onto the retina required for clear vision. In the event of an injury, the cornea is equipped with many strategies contributing to competent wound healing, including angiogenic and immune privileges, and mechanotransduction. Various factors, including growth factors, keratin, cytokines, integrins, crystallins, basement membrane, and gap junction proteins are involved in CE wound healing and serve as markers in the healing process. Studies of CE wound healing are advancing rapidly in tandem with the rise of corneal bioengineering, which employs limbal epithelial stem cells as the primary source of cells utilizing various types of biomaterials as substrates.

Citing Articles

Therapeutic Assessment of Diverse Doxycycline-Based Formulations in Promoting Deep Corneal Wound Healing: Evidence from a Rat Model.

Chan S, Tseng C, Huang W, Lin C Vet Sci. 2025; 12(2).

PMID: 40005905 PMC: 11860526. DOI: 10.3390/vetsci12020143.

Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.

Gupta S, Zhang E, Sinha S, Martin L, Varghese T, Forck N Mol Vis. 2025; 30:448-464.

PMID: 39959170 PMC: 11829792.

Advancements in Hydrogels for Corneal Healing and Tissue Engineering.

Wu K, Qian S, Faucher A, Tran S Gels. 2024; 10(10).

PMID: 39451315 PMC: 11507397. DOI: 10.3390/gels10100662.

Remarkable improvement of symptoms and signs of severe dry eye treated by ocular immersion hydrotherapy.

Tao Y, Cui H, Zhang S, Zhang T Clin Case Rep. 2024; 12(7):e9182.

PMID: 39005574 PMC: 11245401. DOI: 10.1002/ccr3.9182.

Aberrations in Cell Signaling Quantified in Diabetic Murine Globes after Injury.

Azzari N, Segars K, Rapaka S, Kushimi L, Rich C, Trinkaus-Randall V Cells. 2024; 13(1).

PMID: 38201230 PMC: 10778404. DOI: 10.3390/cells13010026.

References

Guan J, Zhou L, Wang L, Li X, Pan Z . Germinal peptide eye drops promote corneal wound healing and decrease inflammation after alkali injury. Exp Eye Res. 2020; 199:108191. DOI: 10.1016/j.exer.2020.108191. View

Tighe S, Moein H, Chua L, Cheng A, Hamrah P, Tseng S . Topical Cryopreserved Amniotic Membrane and Umbilical Cord Eye Drops Promote Re-Epithelialization in a Murine Corneal Abrasion Model. Invest Ophthalmol Vis Sci. 2017; 58(3):1586-1593. DOI: 10.1167/iovs.16-20834. View

Miyagi H, Thomasy S, Russell P, Murphy C . The role of hepatocyte growth factor in corneal wound healing. Exp Eye Res. 2017; 166:49-55. PMC: 5831200. DOI: 10.1016/j.exer.2017.10.006. View

Yoshioka R, Shiraishi A, Kobayashi T, Morita S, Hayashi Y, Higashiyama S . Corneal epithelial wound healing impaired in keratinocyte-specific HB-EGF-deficient mice in vivo and in vitro. Invest Ophthalmol Vis Sci. 2010; 51(11):5630-9. DOI: 10.1167/iovs.10-5158. View

Sotozono C, He J, Matsumoto Y, Kita M, Imanishi J, Kinoshita S . Cytokine expression in the alkali-burned cornea. Curr Eye Res. 1997; 16(7):670-6. DOI: 10.1076/ceyr.16.7.670.5057. View

Wu J, Kent I, Shekhar N, Chancellor T, Mendonca A, Dickinson R . Actomyosin pulls to advance the nucleus in a migrating tissue cell. Biophys J. 2014; 106(1):7-15. PMC: 3907209. DOI: 10.1016/j.bpj.2013.11.4489. View

Tolino M, Block E, Klarlund J . Brief treatment with heparin-binding EGF-like growth factor, but not with EGF, is sufficient to accelerate epithelial wound healing. Biochim Biophys Acta. 2011; 1810(9):875-8. PMC: 3143286. DOI: 10.1016/j.bbagen.2011.05.011. View

Wang L, Gonzalez S, Dai W, Deng S, Lu L . Effect of Hypoxia-regulated Polo-like Kinase 3 (Plk3) on Human Limbal Stem Cell Differentiation. J Biol Chem. 2016; 291(32):16519-29. PMC: 4974368. DOI: 10.1074/jbc.M116.725747. View

Zhang Y, Gao N, Wu L, Lee P, Me R, Dai C . Role of VIP and Sonic Hedgehog Signaling Pathways in Mediating Epithelial Wound Healing, Sensory Nerve Regeneration, and Their Defects in Diabetic Corneas. Diabetes. 2020; 69(7):1549-1561. PMC: 7306128. DOI: 10.2337/db19-0870. View

10.

Saghizadeh M, Kramerov A, Svendsen C, Ljubimov A . Concise Review: Stem Cells for Corneal Wound Healing. Stem Cells. 2017; 35(10):2105-2114. PMC: 5637932. DOI: 10.1002/stem.2667. View

11.

Liu C, Whei-Yang Kao W . Corneal Epithelial Wound Healing. Prog Mol Biol Transl Sci. 2015; 134:61-71. DOI: 10.1016/bs.pmbts.2015.05.002. View

12.

McBain V, Forrester J, McCaig C . HGF, MAPK, and a small physiological electric field interact during corneal epithelial cell migration. Invest Ophthalmol Vis Sci. 2003; 44(2):540-7. DOI: 10.1167/iovs.02-0570. View

13.

Yu F, Yin J, Xu K, Huang J . Growth factors and corneal epithelial wound healing. Brain Res Bull. 2009; 81(2-3):229-35. PMC: 3010187. DOI: 10.1016/j.brainresbull.2009.08.024. View

14.

Barrera V, Troughton L, Iorio V, Liu S, Oyewole O, Sheridan C . Differential Distribution of Laminin N-Terminus α31 Across the Ocular Surface: Implications for Corneal Wound Repair. Invest Ophthalmol Vis Sci. 2018; 59(10):4082-4093. PMC: 6735649. DOI: 10.1167/iovs.18-24037. View

15.

Notara M, Lentzsch A, Coroneo M, Cursiefen C . The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure. Stem Cells Int. 2018; 2018:8620172. PMC: 5964490. DOI: 10.1155/2018/8620172. View

16.

Yang L, Zhang S, Duan H, Dong M, Hu X, Zhang Z . Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice. Stem Cells Transl Med. 2018; 8(1):46-57. PMC: 6312447. DOI: 10.1002/sctm.18-0005. View

17.

Colabelli Gisoldi R, Pocobelli A, Villani C, Amato D, Pellegrini G . Evaluation of molecular markers in corneal regeneration by means of autologous cultures of limbal cells and keratoplasty. Cornea. 2010; 29(7):715-22. DOI: 10.1097/ICO.0b013e3181c91ac4. View

18.

Liu J, Xue Y, Dong D, Xiao C, Lin C, Wang H . CCR2 and CCR2 corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion. Mucosal Immunol. 2017; 10(5):1145-1159. PMC: 5562841. DOI: 10.1038/mi.2016.139. View

19.

Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J . Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med. 2011; 208(5):1083-92. PMC: 3092349. DOI: 10.1084/jem.20092277. View

20.

Ker-Woon C, Ghafar N, Hui C, Mohd Yusof Y, Wan Ngah W . The effects of acacia honey on in vitro corneal abrasion wound healing model. BMC Cell Biol. 2015; 16:2. PMC: 4340287. DOI: 10.1186/s12860-015-0053-9. View