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Review
.2017 Jun 12;18(6):1257.
doi: 10.3390/ijms18061257.

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities

Affiliations
Review

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities

Anne Bukowiecki et al. Int J Mol Sci..

Abstract

The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

Keywords: cornea; inflammation; regeneration; repair; skin; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Parallels and differences in corneal and skin wound healing. Injury and wound healing in cornea and skin involves a similar sequence of events: inflammation, myofibroblast differentiation, extracellular matrix (ECM) deposition and eventually development of fibrosis. Yet, specific cellular responses, such as immediate keratocyte apoptosis after wounding, are unique events in corneal wound healing and presumably serve to avoid excessive corneal inflammatory reactions and opacification after tissue injury. Due to the physiological avascular nature of the cornea, hemostasis and activation of platelets are absent in corneal healing; however, both processes provide an important source of growth factors and cytokines in skin wound healing. Instead, in cornea, several of these factors (e.g., platelet-derived growth factor (PDGF)) are provided by epithelial cells [17]. Furthermore, to maintain its transparency, the cornea does not respond with the induction of capillary sprouts to minor injuries, which is essential to maintain good vision; however, chronic injury leads to an angiogenic response. (A) Histological view of the unwounded mouse cornea (HE staining); Ep: epithelium; BM: Bowman layer; St: stroma; DM: Descemet’s membrane; En: endothelium; (B) Histological view of the unwounded mouse skin (HE staining); EP: epidermis; PD: papillary dermis; RD: reticular dermis; Pc: panniculus carnosus; HF: hair follicle; (C) Infiltration of inflammatory cells into the physiologically avascular cornea and sprouting of blood and lymphatic vessels from the limbus after severe corneal injury (modified from Hos et al. [18]). Of note, corneal angiogenesis is a rare event and usually does not occur during wound healing. However, in severe and eye-threatening conditions, proangiogenic stimuli might overcome the corneal antiangiogenic mechanisms and lead to the secondary ingrowth of pathological vessels from the limbus into the corneal center. This is in contrast to skin wound healing, where capillary sprouts are important for an adequate healing response; (D) In skin wound healing, hemostasis, platelet activation and angiogenesis are key repair mechanisms. Similar to corneal wound healing, skin repair involves immune cell recruitment, activation and transdifferentiation of fibroblasts, which synthesize and remodel extracellular matrix and mediate wound contraction; (E) Murine corneal whole mount after experimentally-induced corneal injury and neovascularization (green: blood vessels, CD31 stain; red: lymphatic vessels, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) stain); the dashed white line indicates the limbal border. (F) Skin wound three days post-injury; immunohistochemical double staining for fibrin and blood vessels (blue: DAPI stain; red: fibrin stain; green: blood vessels, CD31 stain).
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