Molecular Insights into Corneal Wound Healing and Inflammation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 6288

Special Issue Editor


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Guest Editor
Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
Interests: neuroimmune crosstalk mediation of corneal inflammation; potential pharmaceutical treatment against corneal fibrosis; immunotherapy strategies to suppress corneal angiogenesis; modulation of corneal transplant immunity; novel cell-based therapies; corneal tissue engineering and regeneration; new insights in refractive surgery

Special Issue Information

Dear Colleagues,

During its evolution, the cornea has developed an exclusive process of wound healing designed to maintain and regenerate the tissue while preserving its transparency. Despite its similarities to other tissues such as skin, the cornea is characterized by a lack of vessels, dense sensory innervation, and a specific population of immune resident cells, making it a specialized tissue that requires a high level of scientific attention. The active crosstalk between sensory nerves and immune cells is essential for maintaining its avascularity, transparency, and immune privilege; however, alterations in the environment caused by trauma, infection, ocular surface diseases, or surgery trigger the cornea to undergo an active healing process, first to maintain the external barrier of the eye and then to restore its transparency and sensory functions. Multiple cellular events involving cell death, proliferation, migration, differentiation, and extracellular matrix remodeling are orchestrated to effectively repair the damaged tissue; however, the final resolution of the wound healing is a much more complex process in which inflammatory mediators are key components that mediate the balance between full restoration of the corneal integrity and functionality, or fibrosis. While a suitable inflammatory reaction is necessary for infection eradication and proper wound healing, exacerbated inflammation is the main trigger of edema, fibrosis, and loss of sensory function. Despite numerous advances in managing corneal wound healing, inflammatory-related complications such as ocular pain, fibrosis, diabetic keratopathies, dry eye, graft failure, viral infections, or dystrophies, among many others, remain the main public health concerns. In this Special Issue, we welcome all types of manuscripts from both basic and clinical research aimed at elucidating new strategies for modulating the inflammatory response while promoting the restoration of the cornea’s intrinsic functions.

Dr. Tomas Blanco
Guest Editor

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Keywords

  • corneal wound healing
  • corneal transplantation
  • sensory nerves
  • neovascularization
  • fibrosis
  • growth factors
  • cytokines
  • neuropeptides

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Published Papers (2 papers)

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Research

23 pages, 3969 KiB  
Article
Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet’s Stripping Only Model
by Mohit Parekh, Annie Miall, Ashley Chou, Lara Buhl, Neha Deshpande, Marianne O. Price, Francis W. Price and Ula V. Jurkunas
Cells 2024, 13(14), 1218; https://doi.org/10.3390/cells13141218 - 19 Jul 2024
Cited by 4 | Viewed by 2300
Abstract
Descemet’s Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We [...] Read more.
Descemet’s Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor (SNAI1/2) and Vimentin (VIM) while decreasing Cadherin (CDH1), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet’s membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance. Full article
(This article belongs to the Special Issue Molecular Insights into Corneal Wound Healing and Inflammation)
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16 pages, 6456 KiB  
Article
Effects of Diabetes Mellitus on Corneal Immune Cell Activation and the Development of Keratopathy
by Pier Luigi Surico, Akitomo Narimatsu, Katayoon Forouzanfar, Rohan Bir Singh, Sara Shoushtari, Reza Dana and Tomas Blanco
Cells 2024, 13(6), 532; https://doi.org/10.3390/cells13060532 - 18 Mar 2024
Cited by 5 | Viewed by 3304
Abstract
Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has [...] Read more.
Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45+CD11b+Ly-6G myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1β, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm2 in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK. Full article
(This article belongs to the Special Issue Molecular Insights into Corneal Wound Healing and Inflammation)
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