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Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models.

Wang X, Huang Y, Jastaneiah S, Majumdar S, Kang JU, Yiu SC, Stark W, Elisseeff JH - PLoS ONE (2015)

Bottom Line: The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system.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.

View Article: PubMed Central - PubMed

Affiliation: Wilmer 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.

No MeSH data available.


Related in: MedlinePlus

The optical coherence tomography (OCT) aspects of different corneal ectatic models after corsslinking and swelling.(A) Corneas were preserved in 15% dextran, and (B) Corneas were preserved in DMEM for 4 hours.
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pone.0136999.g002: The optical coherence tomography (OCT) aspects of different corneal ectatic models after corsslinking and swelling.(A) Corneas were preserved in 15% dextran, and (B) Corneas were preserved in DMEM for 4 hours.

Mentions: Enzyme treatments of rabbit corneas ex vivo resulted in corneal surface erosion and corneal thinning, as characterized by OCT (Fig 2A). The mean corneal center thickness (CCT) before and after enzyme treatment and crosslinking are listed in Table 1. The control group had a thickness of 362±12.0 μm. COLG treatment resulted in corneal thinning to 331±10.5 μm and surface erosion, and ChaseABC treatment decreased the corneal thickness to 316±6.5 μm. UVA crosslinking resulted in corneal thinning in all samples compared with Non-CXL ones. CXL and CXL+Col smoothened the corneal surface. In all the CXL+Col groups, the average central corneal thickness (CCT) was slightly greater in comparison to the conventional CXL samples in the same treatment group. As for the swelling groups (Fig 2B), enzyme treatments decreased the swelling resistance of corneas. Control corneas after swelling in DMEM for 4 hours had an average thickness of 718±7.0 μm (Table 1); COLG treatment increased the swelled thickness to 791±9.5 μm, and ChaseABC treatment resulted in a swelled thickness of 844±12.5 μm. UVA CXL restored the resistance of swelling in both control and ectatic corneas. Furthermore, the CXL+Col groups reduced swelling by 6–17% in comparison to the conventional CXL corneas in the same enzyme treatment group. There was minimal change among the control groups, as crosslinking and treatment with soluble collagen reduced swelling by less then 4%.


Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models.

Wang X, Huang Y, Jastaneiah S, Majumdar S, Kang JU, Yiu SC, Stark W, Elisseeff JH - PLoS ONE (2015)

The optical coherence tomography (OCT) aspects of different corneal ectatic models after corsslinking and swelling.(A) Corneas were preserved in 15% dextran, and (B) Corneas were preserved in DMEM for 4 hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556688&req=5

pone.0136999.g002: The optical coherence tomography (OCT) aspects of different corneal ectatic models after corsslinking and swelling.(A) Corneas were preserved in 15% dextran, and (B) Corneas were preserved in DMEM for 4 hours.
Mentions: Enzyme treatments of rabbit corneas ex vivo resulted in corneal surface erosion and corneal thinning, as characterized by OCT (Fig 2A). The mean corneal center thickness (CCT) before and after enzyme treatment and crosslinking are listed in Table 1. The control group had a thickness of 362±12.0 μm. COLG treatment resulted in corneal thinning to 331±10.5 μm and surface erosion, and ChaseABC treatment decreased the corneal thickness to 316±6.5 μm. UVA crosslinking resulted in corneal thinning in all samples compared with Non-CXL ones. CXL and CXL+Col smoothened the corneal surface. In all the CXL+Col groups, the average central corneal thickness (CCT) was slightly greater in comparison to the conventional CXL samples in the same treatment group. As for the swelling groups (Fig 2B), enzyme treatments decreased the swelling resistance of corneas. Control corneas after swelling in DMEM for 4 hours had an average thickness of 718±7.0 μm (Table 1); COLG treatment increased the swelled thickness to 791±9.5 μm, and ChaseABC treatment resulted in a swelled thickness of 844±12.5 μm. UVA CXL restored the resistance of swelling in both control and ectatic corneas. Furthermore, the CXL+Col groups reduced swelling by 6–17% in comparison to the conventional CXL corneas in the same enzyme treatment group. There was minimal change among the control groups, as crosslinking and treatment with soluble collagen reduced swelling by less then 4%.

Bottom Line: The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system.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.

View Article: PubMed Central - PubMed

Affiliation: Wilmer 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.

No MeSH data available.


Related in: MedlinePlus