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Title

Establishing Corneal Cross-Linking With Riboflavin and UV-A in the Mouse Cornea In Vivo: Biomechanical Analysis
Authors
Hammer, Arthur
Kling, Sabine
Boldi, Marc-Olivier
Richoz, Olivier
Tabibian, David
Randleman, J. Bradley
Hafezi, Farhad
Published in Investigative Ophthalmology & Visual Science. 2015, vol. 56, no. 11, p. 6581
Abstract Purpose: To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea in vivo and to develop tools to measure the biomechanical changes observed. Methods: A total of 55 male C57BL/6 wild-type mice (aged 5 weeks) were divided into 14 groups. Standard CXL parameters were adapted to the anatomy of the mouse cornea, and riboflavin concentration (0.1%–0.5%) and fluence series (0.09–5.4 J/cm2) were performed on the assumption of the endothelial damage thresholds. Untreated and riboflavin only corneas were used as controls. Animals were killed at 30 minutes and at 1 month after CXL. Corneas were harvested. Two-dimensional (2D) biomechanical testing was performed using a customized corneal holder in a commercially available stress-strain extensometer/indenter. Both elastic and viscoelastic analyses were performed. Statistical inference was performed using t-tests and specific mathematical models fitted to the experimental stress-strain and stress-relaxation data. Adjusted P values by the method of Benjamini and Hochberg are reported. Results: For all CXL treatment groups, stress-relaxation showed significant differences (P < 0.0001) after 120 seconds of constant strain application, with cross-linked corneas maintaining a higher stress (441 ± 40 kPa) when compared with controls (337 ± 39 kPa). Stress-strain analysis confirmed these findings but was less sensitive to CXL-induced changes: at 0.5% of strain, cross-linked corneas remained at higher stress (778 ± 111 kPa) when compared with controls (659 ± 121 kPa). Conclusions: Cross-linking was induced in the mouse cornea in vivo, and its biomechanical effect successfully measured. This could create opportunities to study molecular pathways of CXL in transgenic mice.
Keywords Animals — Biomechanical Phenomena — Cornea/drug effects/physiopathology/radiation effects — Cross-Linking Reagents/pharmacology — Disease Models — Animal — Keratoconus/drug therapy/physiopathology — Male — Mice — Mice — Inbred C57BL — Photosensitizing Agents/pharmacology — Riboflavin/pharmacology — Ultraviolet Rays
Identifiers
PMID: 26465887
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Article (Published version) (1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques
Faculté d'économie et de management / Research Center for Statistics
Citation
(ISO format) 		HAMMER, Arthur et al. Establishing Corneal Cross-Linking With Riboflavin and UV-A in the Mouse Cornea In Vivo: Biomechanical Analysis. In: Investigative Ophthalmology & Visual Science, 2015, vol. 56, n° 11, p. 6581. doi: 10.1167/iovs.15-17426 https://archive-ouverte.unige.ch/unige:79867

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Deposited on : 2016-01-22

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