Differential Gene Transcription of Extracellular Matrix Components in Response to In Vivo Corneal Crosslinking (CXL) in Rabbit Corneas

Differential Gene Transcription of Extracellular Matrix Components in Response to In Vivo Corneal Crosslinking (CXL) in Rabbit Corneas

Author Kling, Sabine Google Scholar
Hammer, Arthur Google Scholar
Torres Netto, Emilio A. Autor UNIFESP Google Scholar
Hafezi, Farhad Google Scholar
Abstract Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit cornea in vivo and identified potential molecular signaling pathways. Methods: A total of 15 corneas of eight male New-Zealand-White rabbits were deepithelialized and equally divided into five groups. Group 1 served as an untreated control. Groups 2 to 5 were soaked with 0.1% riboflavin for 20 minutes, which in Groups 3 to 5 was followed by UV-A irradiation at a fluence of 5.4 J/cm(2). Ultraviolet A (UVA) irradiation was delivered at 3 mW/cm(2) for 30 minutes (Group 3, standard CXL protocol), 9 mW/cm(2) for 10 minutes (Group 4, accelerated), and 18 mW/cm(2) for 5 minutes (Group 5, accelerated). At 1 week after treatment, corneal buttons were obtained; mRNA was extracted and subjected to cDNA sequencing (RNA-seq). Results: A total of 297 differentially transcribed genes were identified after CXL treatment. CXL downregulated extracellular matrix components (collagen types 1A1, 1A2, 6A2, 11A1, keratocan, fibromodulin) and upregulated glycan biosynthesis and proteoglycan glycosylation (GALNT 3, 7, and 8, B3GALT2). Also, CXL activated pathways related to protein crosslinking (transglutaminase 2 and 6). In 9.1% of the significantly different genes, CXL at 3 mW/cm(2) (Group 1) induced a more distinct change in gene transcription than the accelerated CXL protocols, which induced a lower biomechanical stiffening effect. Conclusions: Several target genes have been identified that might be related to the biomechanical stability and shape of the cornea. Stiffening-dependent differential gene transcription suggests the activation of mechano-sensitive pathways.
Keywords corneal crosslinking
differential transcription
glycosylation
extracellular matrix
corneal biomechanics
xmlui.dri2xhtml.METS-1.0.item-coverage Rockville
Language English
Sponsor Gelbert Foundation (Geneva, Switzerland)
Date 2017
Published in Translational Vision Science & Technology. Rockville, v. 6, n. 6, p. -, 2017.
ISSN 2164-2591 (Sherpa/Romeo, impact factor)
Publisher Assoc Research Vision Ophthalmology Inc
Extent -
Origin http://dx.doi.org/10.1167/tvst.6.6.8
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000425360100008
URI https://repositorio.unifesp.br/handle/11600/58189

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