Chemical Cross-Linking of Corneal Tissue to Reduce Progression of Loss of Sight in Patients With Keratoconus



Haneef, Atikah ORCID: 0000-0001-7422-9594, Gopalan, Ramprasad Obula Giridhara, Rajendran, Divya T, Nunes, Jessica, Kuppamuthu, Dharmalingam, Radhakrishnan, Naveen, Young, Tai-Horng, Hsieh, Hao-Ying, Prajna, Namperumalsamy Venkatesh, Willoughby, Colin E
et al (show 1 more authors) (2021) Chemical Cross-Linking of Corneal Tissue to Reduce Progression of Loss of Sight in Patients With Keratoconus. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, 10 (5). 6-.

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Abstract

<h4>Purpose</h4>We aimed to develop a novel chemical cross-linker treatment for keratoconus by reacting dicarboxylic acid spacer molecules and amine functional groups on protein structure of the tissue using carbodi-imide chemistry. We propose this as an alternative to conventional cross-linking treatment for keratoconus.<h4>Methods</h4>The study involved optimization of the cross-linker formulation. Mechanical stiffness of ex vivo porcine and human corneas after application of the cross-linker was measured. Histochemical analysis was performed to record changes in gross morphology after cross-linker treatment on ex vivo porcine and human and in vivo rabbit corneas. Terminal deoxynucleotidyl transferase-mediated dUTP-X nick-end-labeling (TUNEL) staining was performed to study apoptotic effects of cross-linker. Cytotoxicity potential of cross-linker was evaluated by studying explant cultures for cellular outgrowth and immunostaining assays on porcine and human corneas after treatment.<h4>Results</h4>We demonstrated a clinically relevant increase in stiffness in ex vivo experiments using porcine and human cornea without removal of corneal epithelium. Histological analysis showed no change in gross morphology of cornea and no evidence of apoptosis. In vivo treatment of rabbit eyes demonstrated initial thinning of corneal epithelium that recovered after seven days although with abnormal regularity of cells. Cellular outgrowth from corneal explant cultures after treatment further confirmed cell survival after treatment.<h4>Conclusions</h4>This chemical cross-linking of corneal tissue has potential advantages over current therapeutic options including lower cytotoxicity to stromal cells than ultraviolet A treatment.<h4>Translational relevance</h4>The cross-linker has potential to become a treatment for keratoconus because it overcomes the need for procedures using specialized equipment and ensures accessibility to large populations.

Item Type: Article
Uncontrolled Keywords: cross-linking, cornea, collagen, keratoconus, carbodi-imide chemistry
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 30 Apr 2021 08:39
Last Modified: 15 Mar 2024 07:52
DOI: 10.1167/tvst.10.5.6
Open Access URL: https://tvst.arvojournals.org/article.aspx?article...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3121091