Chondroitin Sulfate–Based Biocompatible Crosslinker Restores Corneal Mechanics and Collagen Alignment

作者：Xiaokun Wang, Shoumyo Majumdar, Garret Ma, Jeeyeon Sohn, Samuel C. Yiu, Walter J. Stark, Awad Al-Qarni, Deepak P. Edward, Jennifer H. Elisseeff · 发表于：Investigative Ophthalmology & Visual Science · 年份：2017 · DOI：10.1167/iovs.16-21292 · 被引用次数：30 · 研究领域：Corneal Surgery and Treatments、Proteoglycans and glycosaminoglycans research、Corneal surgery and disorders

Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's modulus, and ultrastructure of the crosslinked corneas were characterized. In addition, rabbit corneas were further treated with a collagenase-chondroitinase solution to create an ex vivo keratoconus (KC)-like model. The KC model corneas were crosslinked with a standard riboflavin-ultraviolet (UV) method or alternatively with CS-NHS. Corneal mechanics, ultrastructure, and keratocyte gene expression were evaluated after UV and CS-NHS crosslinking. Results: CS-NHS effectively penetrated into the corneal stroma within 60 minutes of treatment initiation. CS-NHS crosslinking reduced the swelling ratio by 35%, increased Young's modulus by 20%, and increased collagen fibril diameter and density. CS-NHS crosslinking improved corneal mechanics of KC model corneas to levels comparable to those with UV crosslinking. Moreover, CS-NHS crosslinking demonstrated significant downregulation of proinflammatory gene expression of keratocytes, indicating a potential protective effect imparted by CS-NHS during crosslinking. Conclusions: Our results demonstrated that CS-NHS can reinforce normal and KC model corneal me...