Correlation Between Epithelial Ingrowth and Basement Membrane Remodeling in Human Corneas After Laser-Assisted In Situ Keratomileusis

Fournié, Pierre; Gordon, Gabriel M.; Dawson, Daniel G.; Malecaze, François; Edelhauser, Henry F.; Fini, M. Elizabeth

doi:10.1001/archophthalmol.2010.23

Cited by 13 publications

(6 citation statements)

References 49 publications

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“…Contrary to PRK, LASIK does not involve significant stromal remodeling except at the flap margin, and haze is generally absent. Myofibroblasts also appear transiently mainly at the flap margin, where hypercellularity and epithelial ingrowth are usually noted even in uneventful cases (Ivarsen et al, 2003; Fournié et al, 2010). The flap margin also displays increased MMP production and long-term accumulation of fibrotic ECM consisting of several collagens, various basement membrane components and tenascin-C, apparently reinforcing flap adhesion (Azar et al, 1998; Pérez-Santonja et al, 1998; Wachtlin et al, 1999; Maguen et al, 2007; 2008; Esquenazi et al, 2009).…”

Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

628

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

628

554

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“…In surgeries such as LASIK or photorefractive keratectomy (PRK), any ocular surface disease can be made worse by the procedure and can result in serious complications. 39 Additionally, the reduction in tear function after LASIK may lead to an increase in the concentration of proinflammatory cytokines and MMP-9 in the tear film, which results in dry eyes and insufficient attachment between the corneal flap and the corneal bed. 16 MMP-9 has been implicated in poor epithelial healing, and epithelial ingrowth after LASIK surgery.…”

Section: Mmp-9 In Lasik and Other Ocular Surgerymentioning

confidence: 99%

The Practical Detection of MMP-9 Diagnoses Ocular Surface Disease and May Help Prevent Its Complications

Kaufman

2013

Cornea

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A rapid in-office test that is sensitive for identifying inflammatory dry eye and ocular surface disease may facilitate better preoperative management of the ocular surface. Optimization of the ocular surface perioperatively would be expected to reduce complications from laser in situ keratomileusis and other surgeries that often make the underlying disease worse. This test may also indicate the need for antiinflammatory therapies, such as cyclosporine or steroids, and also may predict those patients who are more likely to respond.

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“…The provenance of SM-induced intra-corneal epithelial cells is unknown, but may result from several factors, including a mechanically weakened BM, profound corneal edema, and wound healing processes in the anterior stroma. These islands may result in corneal pathologies through disruption of light refraction or induction of stromal degradation through the release of disruptive signaling mediators [21], [34], [35], [36]. In this study, epithelial islands had no apparent continuity with the corneal surface epithelium and are therefore distinct from epithelial ingrowth beneath corneal flaps (such as can occur following laser-assisted in situ keratomileusis) [37].…”

Section: Discussionmentioning

confidence: 84%

Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

et al. 2012

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A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to that observed in human casualties. However, a better understanding of the temporal changes that occur during the biphasic SM injury is crucial to mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of pathogenesis of the chronic SM injury over eight weeks. We confirm that MGK onset exhibits a biphasic trajectory involving corneal surface regeneration over the first two weeks, followed by the rapid development and progressive degeneration of corneal structure. Preclinical markers of corneal dysfunction were identified, including destabilization of the basal corneal epithelium, basement membrane zone abnormalities and stromal deformation. Clinical sequelae of MGK appeared abruptly three weeks after exposure, and included profound anterior edema, recurring corneal erosions, basement membrane disorganization, basal cell necrosis and stromal degeneration. Unlike resolved corneas, MGK corneas exhibited frustrated corneal wound repair, with significantly elevated histopathology scores. Increased lacrimation, disruption of the basement membrane and accumulation of pro-inflammatory mediators in the aqueous humor provide several mechanisms for corneal degeneration. These data suggest that the chronic injury is fundamentally distinct from the acute lesion, involving injury mechanisms that operate on different time scales and in different corneal tissues. Corneal edema appears to be the principal pathology of MGK, in part resulting from persistent necrosis of the basal corneal epithelium and deterioration of the basement membrane. The findings also provide a potential explanation as to why administration of anti-inflammatories transiently delays, but does not prevent, the development of MGK sequelae.

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Correlation Between Epithelial Ingrowth and Basement Membrane Remodeling in Human Corneas After Laser-Assisted In Situ Keratomileusis

Cited by 13 publications

References 49 publications

Progress in corneal wound healing

Progress in corneal wound healing

The Practical Detection of MMP-9 Diagnoses Ocular Surface Disease and May Help Prevent Its Complications

Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

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