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Growth factors in tympanic membrane perforations
T Somers1, G Goovaerts, L Schelfhout
1University Department of Otolaryngology, Sint-Augustinus Hospital, Antwerp, Belgium.
Objective:
Little is known about the arrested healing of chronic central tympanic membrane perforations and the mechanism involved in this process. Some authors have traced the failure to a growth factor deficiency at the perforation margin. In addition, recently, several growth factors have been tried out to improve tympanic membrane (TM) closure in animals. The authors sought to determine the expression of some well-known growth factor peptides in normal human TM and in TMs with a chronic central perforation.
Materials And Methods:
Total TM specimens were obtained from patients with a normal TM (N = 10) soon after death and from patients with a chronic perforation (N = 20) undergoing myringoplasty with use of an allograft TM. Formaldehyde solution-fixed TMs were analyzed after immunohistochemical staining using highly purified monoclonal antibodies to determine whether epidermal growth factor receptor (EGF-r), transforming growth factor-alpha (TGF-alpha), basic fibroblast growth factor (b-FGF), or transforming growth factor-beta 1 (TGF-beta 1) was expressed in the TMs.
Results:
The distribution pattern for EGF-r, TGF-alpha, and b-FGF was similar in perforated and nonperforated TMs. In contrast to this, TGF-beta 1 staining was markedly different in perforated and nonperforated TMs. No or minimal TGF-beta 1 was observed in normal TMs, whereas TGF-beta 1 staining was prominent in perforated membranes, mostly at the perforation border.
Conclusions:
The authors experimental findings imply that EGF-r, b-FGF, and TGF-alpha expression are not significantly different in TMs with and without a central chronic perforation. However, for TGF-beta 1, the authors found an increased staining pattern in perforated TMs when compared with that of normal TMs, and staining at the fibrotic and scarred perforation margin was pronounced. Based on these findings, the authors speculate on the possible role of TGF-beta 1 in the development of the fibrotic scar at the perforation margin explaining the deficient healing pattern of tympanic membranes in chronic otitis media. Possible clinical implications for the future, including growth factor therapy, are discussed.
Insights
Chronic tympanic membrane perforations show increased transforming growth factor-beta 1 (TGF-beta 1) at the perforation site, unlike normal eardrums. This suggests TGF-beta 1 may contribute to the scarring that hinders healing in chronic otitis media.
Area of Science:
- Otolaryngology
- Regenerative Medicine
- Cell Biology
Background:
- Chronic tympanic membrane perforations often fail to heal, a process potentially linked to growth factor imbalances.
- Previous studies suggest growth factor deficiency at the perforation margin may impede healing.
- Animal models have shown promise in using growth factors to enhance tympanic membrane (TM) closure.
Purpose of the Study:
- To investigate the expression of key growth factor peptides in normal human TMs versus those with chronic central perforations.
- To identify potential molecular mechanisms underlying the arrested healing of chronic tympanic membrane perforations.
Main Methods:
- Human TM specimens from 10 normal individuals and 20 patients with chronic perforations were analyzed.
- Immunohistochemical staining was performed on formaldehyde-fixed TMs.
- Monoclonal antibodies were used to detect the expression of epidermal growth factor receptor (EGF-r), transforming growth factor-alpha (TGF-alpha), basic fibroblast growth factor (b-FGF), and transforming growth factor-beta 1 (TGF-beta 1).
Main Results:
- Expression patterns of EGF-r, TGF-alpha, and b-FGF were similar in both normal and perforated TMs.
- Transforming growth factor-beta 1 (TGF-beta 1) showed significantly different expression.
- Minimal TGF-beta 1 was found in normal TMs, while perforated TMs exhibited prominent TGF-beta 1 staining, particularly at the perforation border.
Conclusions:
- EGF-r, b-FGF, and TGF-alpha expression do not appear to differ significantly between normal and chronically perforated TMs.
- Increased TGF-beta 1 expression in perforated TMs, especially at the fibrotic scar margin, suggests a role in impaired healing.
- These findings may elucidate the mechanism of deficient healing in chronic otitis media and suggest potential therapeutic targets, such as TGF-beta 1 modulation.
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