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Targeting Corneal Wound Healing: Molecular Access to Diagnosis, Pathophysiology, and Treatment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 March 2025) | Viewed by 3222

Special Issue Editor

Special Issue Information

Dear Colleagues,

The wound healing of the cornea decides over the optical visual performance of the eye after incidents. After injury, a quick and complete recovery is desired, albeit after laser surgery a smooth non-regenerative tissue adaption is the target, providing the desired optically perfect outcome without relapse of refractive imperfection. The aim of corneal decides over how corneal wound healing is launched, processed, directed, and finally, stopped. We have come a long way since the initial detection of extracellular matrix components (such as fibronectins, tenascin, etc.), enzymatic activities (such as plasmin), and growth factors (such as EGF, bFGF, etc.) these crucial proteins that were later on called cytokines. Today available at the edge sophisticated techniques, showing unknown precision and diagnostic accuracy have revealed many this far hidden paths of cellular behaviour and control, each offering a new window of understanding and potential therapy – down to the very molecular level. This special issue on this timely so very active area is intended to offer you a platform to present your expertise and data to others, contributing to the progress in the field and a better future for our patients.

Dr. Gysbert van Setten
Guest Editor

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Keywords

  • corneal wound healing
  • optical visual performance
  • cornea
  • extracellular matrix
  • enzymatic activities
  • growth factors
  • cytokines

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Published Papers (2 papers)

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Research

22 pages, 4074 KiB  
Article
Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts
by Divya Subramanian, Nathaniel S. Tjahjono, Satweka Nammi, Miguel Miron-Mendoza, Victor D. Varner, W. Matthew Petroll and David W. Schmidtke
Int. J. Mol. Sci. 2025, 26(3), 1183; https://doi.org/10.3390/ijms26031183 - 29 Jan 2025
Viewed by 980
Abstract
Corneal fibroblasts are central to normal and abnormal wound healing in the cornea. During the wound healing process, several biochemical and biophysical signals that are present in the extracellular matrix (ECM) play critical roles in regulating corneal fibroblast behavior. The translocation and activation [...] Read more.
Corneal fibroblasts are central to normal and abnormal wound healing in the cornea. During the wound healing process, several biochemical and biophysical signals that are present in the extracellular matrix (ECM) play critical roles in regulating corneal fibroblast behavior. The translocation and activation of Yes-associated protein (YAP)—a main transcriptional factor in the Hippo signaling pathway—is one example of mechanotransduction involving these signals. However, how corneal fibroblasts integrate these simultaneous cues is unknown. In this study, we utilized well-defined micropatterns of aligned collagen fibrils and other ECM proteins to explore the effects of cell density, topography, geometric confinement, and ECM composition on the translocation of YAP in corneal fibroblasts. We observed that when human corneal fibroblasts (HTKs) were confined to narrow micropatterns (50 μm and 100 μm) of proteins, there was a high degree of cell alignment irrespective of cell seeding density. However, the location of YAP was dependent upon the cell seeding density, ECM composition, and topography. YAP was more nuclear-localized on substrates coated with aligned collagen fibrils or fibronectin as compared to substrates coated with monomeric collagen, random collagen fibrils, or poly-L-Lysine. In addition, we also observed that YAP nuclear localization was significantly reduced when HTKs were cultured on aligned collagen fibrils, monomeric collagen, or fibronectin in the presence of monoclonal blocking antibodies against α5 or β1 integrin subunits. Finally, we observed that HTK cells formed fibrillar fibronectin on both monomeric collagen and aligned collagen fibrils. These findings provide new insights into how simultaneous biochemical and biophysical cues affect YAP localization in corneal fibroblasts. Full article
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12 pages, 1869 KiB  
Article
Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery
by Magdalena Krok, Ewa Wróblewska-Czajka, Olga Łach-Wojnarowicz, Joanna Bronikowska, Zenon P. Czuba, Edward Wylęgała and Dariusz Dobrowolski
Int. J. Mol. Sci. 2024, 25(1), 366; https://doi.org/10.3390/ijms25010366 - 27 Dec 2023
Cited by 1 | Viewed by 1560
Abstract
Background: The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the [...] Read more.
Background: The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the molecular changes occurring after the procedure. Among many cytokines, β-NGF seems to play an important role in the healing processes of corneal damage. Therefore, its role in the regenerative process after CXL treatment may affect the course of treatment and its final results. Tear samples from 52 patients were collected in this prospective study. Additionally, the patients also had a number of tests performed, including corneal topography using optical coherence tomography. Flat (K 1), steep (K 2), cylindrical (CYL), and central corneal thickness (CCT) keratometry were assessed. The tear samples were collected, and other tests were performed before the CXL procedure and afterwards, during the 12-month follow-up period. The NGF concentration was measured using the Bio-Plex Magnetic Luminex Assay. Lower levels of NGF-β were detected in the KC patients than in the control group (p < 0.001). The day after the procedure, the NGF-β level was significantly lower (on average by 2.3 pg/mL) (p = 0.037) than before the procedure, after which, the level of the reagent increases, but only in the group with the advanced cone, one month after CXL it was significantly higher (p = 0.047). Regarding the correlation of NGF with topographic measurements, the following were found: NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 before the CXL procedure; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 one month after CXL; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with CYL nine months after CXL; and, after twelve months, NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K2 and K1. Corneal sensitivity did not statistically and significantly correlate with the level of NGF-β secretion. Our study suggests that NGF may be crucial in the development and progression of KC as well as in the repair mechanisms after CXL surgery. Further research is needed on the role of NGF and other inflammatory biomarkers for rapid diagnosis and selection of targeted therapy in patients with keratoconus. Full article
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