A Systematic Review on Cornea Epithelial-Stromal Homeostasis

Abstract

Introduction: This review aims to summarise the role of different cells, genes, proteins and lipid in regulating cornea epithelial-stromal homeostasis. Methods: We performed an Entrez PubMed literature search using keywords “human,” “cornea,” “epithelial,” “stromal,” “homeostasis,” “fibrosis response,” and “pathogenesis” on 24th of September 2019, resulting in 35 papers, of which 18 were chosen after filtering for “English language” and “published within 10 years” as well as curation for relevance by the authors. Results: The 18 selected papers showed that corneal epithelial cells, fibroblasts and telocytes, together with genes such as Klf4, Pax6 and Id found in the cells, play important roles in achieving homeostasis to maintain corneal integrity and transparency. Proteins classified as pro-fibrotic ligands and anti-fibrotic ligands are responsible for regulating cornea stromal fibrosis and extracellular matrix deposition, thus regulators of scar formation during wound healing. Anti-inflammatory ligands and wound repairing ligands are critical in eliciting protective inflammation and promoting epithelial healing, respectively. Protein receptors located on cellular membrane play a role in maintaining intercellular connections as well as corneal hydration. Discussion/Conclusion: These studies prompt development of novel therapeutic strategies such as tear drops or ointments that target certain proteins to maintain corneal homeostasis. However, more in vitro and in vivo studies are required to prove the effectiveness of exogenous administration of molecules in improving healing outcome. Hence, future investigations of the molecular pathways highlighted in this review will reveal novel therapeutic tools such as gene or cell therapy to treat corneal diseases.

The Impaired Wound Healing Process Is a Major Factor in Remodeling of the Corneal Epithelium in Adult and Adolescent Patients With Keratoconus

“…Under physiological conditions, the proper dynamics of cells, cytokines, growth factors, and lipids between the epithelium and the stroma promote epithelial integrity and protective inflammation, as well as limiting corneal fibrosis. 92 , 93 In KTCN, the physiological conditions of cornea biomechanics, dynamic interactions of cells, and homeostasis of cytokines and growth factors are disturbed. In KTCN, the progressive biomechanical weakening of the cornea, being a consequence of changes in collagen fibers and other elements of extracellular matrix in the stroma, contributes to the additional tension of the cornea and results in increased posterior elevation, anterior elevation, and keratometry, as well as decreased corneal thickness.…”

Morphogenetic events influencing corneal maturation, development, and transparency: Light and electron microscopic study

“…VEGF promotes angiogenesis, preserves epithelial-stromal hemostasis, and controls the stromal fibroblast network and corneal integrity (Wong et al, 2021). Although corneal epithelial cells express VEGF in (Ma DH et al, 1999).…”

Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells

“…S2G). At P0 with an early harvest at P6 to capture EmGFP expression that could be lost due to the rapid turnover of the PAX6-positive epithelial cells [101], Ple331 expression was observed throughout the cornea, in the epithelial layer, as well as unexpectedly in the stromal and endothelial layers (Fig. S2G).…”