Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models.
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.
Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Xiaokun
X
Wang
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Yong
Y
Huang
Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Sabah
S
Jastaneiah
Department of Material Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Shoumyo
S
Majumdar
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Jin U
JU
Kang
Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Samuel C
SC
Yiu
Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Walter
W
Stark
Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Department of Material Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Jennifer H
JH
Elisseeff
D000818:Animals; D024042:Collagen Type I / Q000494:pharmacology*; D017364:Collagenases / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D007640:Keratoconus / Q000188:drug therapy / Q000378:metabolism; D023421:Models, Animal; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology; D014466:Ultraviolet Rays; D014792:Visual Acuity / Q000187:drug effects
D024042:Collagen Type I; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D017364:Collagenases; D012256:Riboflavin