ArticlePloS one2013
Hevin plays a pivotal role in corneal wound healing.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Ultrastructural Aspects of Corneal Functional Recovery in Rats Following Intrastromal Keratocyte Injection.Investigative ophthalmology & visual science · 2025Article
- Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.European journal of human genetics : EJHG · 2024Article
- Matricellular proteins in immunometabolism and tissue homeostasis.BMB reports · 2024Review
- Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats.Nature communications · 2024Article
- Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.Investigative ophthalmology & visual science · 2024Article
- Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.Nature communications · 2024Article
- Regenerative Therapy for Corneal Scarring Disorders.Biomedicines · 2024Review
- Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring.International journal of molecular sciences · 2023Article
- Identification of novel therapeutic targets for Fuchs' endothelial corneal dystrophy based on gene bioinformatics analysis.PloS one · 2022Article
- Corneal stromal wound healing: Major regulators and therapeutic targets.The ocular surface · 2021Review
- Immunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children.Infection and immunity · 2020Article
- Immunofibrogenic Gene Expression Patterns in Tanzanian Children with OcularFrontiers in cellular and infection microbiology · 2017Article
- Progress in corneal wound healing.Progress in retinal and eye research · 2015Review
- Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.PLoS neglected tropical diseases · 2015Article
- Nanomedicine approaches for corneal diseases.Journal of functional biomaterials · 2015Review
- The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology.Journal of cell communication and signaling · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin(-/-)) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. METHODOLOGY/PRINCIPAL
findingsWild type (WT) and hevin (-/-) mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin (-/-) mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. CONCLUSIONS/SIGNIFICANCE: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin (-/-) mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing.
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