Radiation Fibrosis of the Vocal Fold: From Man to Mouse

• Type of Material: Article
• Authors: Michael M Johns, Emory University; Vasantha Kolachala, Emory University; Eric Berg, Emory University; Susan Muller, Emory University; Frances X. Creighton, Emory University; Ryan C. Branski, New York University
• Language: English
• Date: 2012-12
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/lary.23735/abstract;jsessionid=A916C02CF6CC3556500503B7BA3A0714.f04t02?systemMessage=Wiley+Online+Library+will+be+disrupted+Saturday%2C+15+March+from+10%3A00-12%3A00+GMT+%2806%3A00-08%3A00+EDT%29+for+essential+maintenance
• Title of Journal or Parent Work: Laryngoscope
• ISSN: 0023-852X
• Volume: 122
• Issue: Suppl 5
• Start Page: S107
• End Page: S125
• Grant/Funding Information: Funding for this project was provided in part by a career development award from Emory University’s NIH Head and Neck Cancer Spore Grant, 5 P50 CA128613-0.
• Keywords: larynx; radiation; fibrosis; dysphonia; vocal fold
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis.