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Updated: Apr 4, 2026
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models
Xiaokun Wang1, Yong Huang2, Sabah Jastaneiah3
1Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Abstract:
Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.
Insights
Researchers developed a new rabbit eye model for keratoconus, a corneal disorder. Adding soluble collagen during UVA crosslinking protected corneal structure and improved treatment outcomes in this novel keratoconus model.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Regenerative Medicine
Background:
- Corneal ectasia, such as keratoconus, presents a significant challenge due to the lack of suitable animal models for studying disease mechanisms and treatment efficacy.
- Current understanding of collagen crosslinking (CXL) mechanisms and its application in treating corneal ectasia is limited by the absence of reliable preclinical models.
Purpose of the Study:
- To establish an ex vivo corneal ectasia model in rabbit eyes that mimics the structural characteristics of human keratoconus.
- To evaluate the protective effects of soluble type I collagen during ultraviolet A (UVA)-based collagen crosslinking in the developed ectatic corneal model.
Main Methods:
- Rabbit corneas were treated with collagenase and chondroitinase to induce ectasia, simulating keratoconus.
- The induced ectatic corneas underwent riboflavin/UVA collagen crosslinking, with and without the addition of soluble type I collagen.
- Corneal morphology, collagen ultrastructure, swelling resistance, and thermal stability were assessed before and after crosslinking treatments.
Main Results:
- Enzyme treatment successfully induced corneal curvature changes, ultrastructural damage, and reduced thermal stability, mirroring keratoconus.
- UVA crosslinking improved swelling resistance and thermal stability in ectatic corneas, but residual ultrastructural damage persisted.
- The addition of soluble collagen during crosslinking provided significant ultrastructural protection and further enhanced swelling resistance.
Conclusions:
- The developed ex vivo corneal ectasia model effectively replicates key features of human keratoconus.
- This model serves as a valuable platform for investigating the mechanisms of collagen crosslinking and evaluating novel therapeutic strategies for keratoconus.
- Soluble collagen shows promise in enhancing the protective effects and efficacy of UVA crosslinking treatments for corneal ectasia.
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