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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

Transmission electron microscope images of corneal ectatic model before and after crosslinking.Ultrastructure of control rabbit cornea under 9700x magnification. Column from left to right: Control cornea, COLG treated cornea, and ChaseABC treated cornea. Row from top to bottom: Non-CXL, CXL and CXL+ collagen
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pone.0136999.g003: Transmission electron microscope images of corneal ectatic model before and after crosslinking.Ultrastructure of control rabbit cornea under 9700x magnification. Column from left to right: Control cornea, COLG treated cornea, and ChaseABC treated cornea. Row from top to bottom: Non-CXL, CXL and CXL+ collagen

Mentions: Ectatic corneas exposed to COLG or ChaseABC demonstrated collagen ultrastuctural damage in the stroma (Fig 3). In comparison to control corneas, COLG and ChaseABC treatments led to a decrease in fibril density, similar to keratoconus. After crosslinking, Control-CXL showed an increase of fibril density and lamellae condensing compared to non-CXL group, and Control-CXL+Col had a similar effect to the Control-CXL group. In the ectatic corneas, UVA crosslinking revealed ultrastructural damages. In the COLG-CXL group, although UVA crosslinking increased the fibril density in the stroma, large tears between the collagen lamellae and keratocytes were noted. In the ChaseABC-CXL group, gaps between lamellae existed after UVA crosslinking. When soluble collagen was added in the crosslinking system, no tear between keratocytes and lamellae in the COLG-CXL+Col group, and no gaps between the lamellae in the ChaseABC-CXL+Col group were observed, suggesting a protective effect of collagen. The overall morphologies of the collagen ultrastructures in the CXL+Col groups were similar to the uncrosslinked control corneas.


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)

Transmission electron microscope images of corneal ectatic model before and after crosslinking.Ultrastructure of control rabbit cornea under 9700x magnification. Column from left to right: Control cornea, COLG treated cornea, and ChaseABC treated cornea. Row from top to bottom: Non-CXL, CXL and CXL+ collagen
© Copyright Policy
Related In: Results  -  Collection

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

pone.0136999.g003: Transmission electron microscope images of corneal ectatic model before and after crosslinking.Ultrastructure of control rabbit cornea under 9700x magnification. Column from left to right: Control cornea, COLG treated cornea, and ChaseABC treated cornea. Row from top to bottom: Non-CXL, CXL and CXL+ collagen
Mentions: Ectatic corneas exposed to COLG or ChaseABC demonstrated collagen ultrastuctural damage in the stroma (Fig 3). In comparison to control corneas, COLG and ChaseABC treatments led to a decrease in fibril density, similar to keratoconus. After crosslinking, Control-CXL showed an increase of fibril density and lamellae condensing compared to non-CXL group, and Control-CXL+Col had a similar effect to the Control-CXL group. In the ectatic corneas, UVA crosslinking revealed ultrastructural damages. In the COLG-CXL group, although UVA crosslinking increased the fibril density in the stroma, large tears between the collagen lamellae and keratocytes were noted. In the ChaseABC-CXL group, gaps between lamellae existed after UVA crosslinking. When soluble collagen was added in the crosslinking system, no tear between keratocytes and lamellae in the COLG-CXL+Col group, and no gaps between the lamellae in the ChaseABC-CXL+Col group were observed, suggesting a protective effect of collagen. The overall morphologies of the collagen ultrastructures in the CXL+Col groups were similar to the uncrosslinked control corneas.

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