Dataset Information

Matrix Metalloproteinase-Deactivating Contact Lens for Corneal Melting.

ABSTRACT: Corneal melting is an uncontrolled, excessive degradation of cellular and extracellular components of the cornea. This potential cause of corneal blindness is caused by excessive expression of zinc-dependent matrix metalloproteinases (MMPs) and has no satisfying cure as of now. Herein, we introduce a novel therapeutic hydrogel which can be made into a contact lens to slow down the progression of corneal melting by deactivating MMPs. The hydrogel backbone is comprised of poly(2-hydroxyetyl methacrylate) (pHEMA), a main material for commercial contact lenses, and dipicolylamine (DPA) which has high affinity and selectivity towards zinc ion. Due to the high affinity towards zinc ions, the DPA-conjugated pHEMA (pDPA-HEMA) hydrogel selectively removes zinc ions from a physiological buffer and deactivates MMP-1, MMP-2 and MMP-9 within 2 hours. pDPA-HEMA hydrogel also effectively prevents degradation of porcine corneas by collagenase A, a zinc-dependent protease, whereas the corneas completely degrades within 15 hours when incubated with pHEMA hydrogel. The presence of pDPA-HEMA hydrogel does not affect the viability of keratocytes and corneal epithelial cells. Unlike the conventional MMP inhibitors (MMPi), the pDPA-HEMA hydrogel minimizes the risk of serious non-specific side effects, and provides a method to slow down the progression of corneal melting and other related ocular diseases.

SUBMITTER: Lopez C

PROVIDER: S-EPMC6831093 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Matrix Metalloproteinase-Deactivating Contact Lens for Corneal Melting.

Lopez Chelsi C Park Shiwha S Edwards Seth S Vong Selina S Hou Shujie S Lee Minyoung M Sauerland Hunter H Lee Jung-Jae JJ Jeong Kyung Jae KJ

ACS biomaterials science & engineering 20190104 3

Corneal melting is an uncontrolled, excessive degradation of cellular and extracellular components of the cornea. This potential cause of corneal blindness is caused by excessive expression of zinc-dependent matrix metalloproteinases (MMPs) and has no satisfying cure as of now. Herein, we introduce a novel therapeutic hydrogel which can be made into a contact lens to slow down the progression of corneal melting by deactivating MMPs. The hydrogel backbone is comprised of poly(2-hydroxyetyl methac ...[more]

PMID: 31692998

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Project description:Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can cause corneal infection (microbial keratitis), with an approximate annualized incidence ranging from ~2 to ~20 cases per 10,000 wearers, and sometimes resulting in permanent vision loss. Research suggests that the pathogenesis of contact lens-associated microbial keratitis is complex and multifactorial, likely requiring multiple conspiring factors that compromise the intrinsic resistance of a healthy cornea to infection. Here, we outline our perspective of the mechanisms by which contact lens wear sometimes renders the cornea susceptible to infection, focusing primarily on our own research efforts during the past three decades. This has included studies of host factors underlying the constitutive barrier function of the healthy cornea, its response to bacterial challenge when intrinsic resistance is not compromised, pathogen virulence mechanisms, and the effects of contact lens wear that alter the outcome of host-microbe interactions. For almost all of this work, we have utilized the bacterium Pseudomonas aeruginosa because it is the leading cause of lens-related microbial keratitis. While not yet common among corneal isolates, clinical isolates of P. aeruginosa have emerged that are resistant to virtually all currently available antibiotics, leading the United States CDC (Centers for Disease Control) to add P. aeruginosa to its list of most serious threats. Compounding this concern, the development of advanced contact lenses for biosensing and augmented reality, together with the escalating incidence of myopia, could portent an epidemic of vision-threatening corneal infections in the future. Thankfully, technological advances in genomics, proteomics, metabolomics and imaging combined with emerging models of contact lens-associated P. aeruginosa infection hold promise for solving the problem - and possibly life-threatening infections impacting other tissues.

Dataset Information

Matrix Metalloproteinase-Deactivating Contact Lens for Corneal Melting.

Publications

Matrix Metalloproteinase-Deactivating Contact Lens for Corneal Melting.

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