Local Alpha1-Antitrypsin Accelerates the Healing of Tympanic Membrane Perforation in Mice.
Laryngoscope
; 134(8): 3802-3806, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38651563
ABSTRACT
BACKGROUND:
Most tympanic membrane (TM) perforations heal spontaneously, but 10%-20% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1-antitrypsin (AAT) is a circulating tissue-protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution.OBJECTIVE:
This study aimed to examine the effects of local clinical-grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation.METHODS:
Wild-type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9 × 10-3 mL at 20 mg/mL on days 0, 1, and 2; n = 15/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post-injury, and TMs were excised for gene analysis by RT-PCR.RESULTS:
There were no adverse reactions in hAAT-treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median 4 and 9, respectively). According to gene expression analysis, VEGF, TGFß, and collagen-5A1 were induced earlier in AAT-treated mice (day 4-5 compared with day 9). Additionally, IL-10 expression levels were higher and IL-6 levels were lower in treated versus untreated mice.CONCLUSION:
A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro-dosing in the format of a single local application. LEVEL OF EVIDENCE NA Laryngoscope, 1343802-3806, 2024.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cicatrización de Heridas
/
Alfa 1-Antitripsina
/
Perforación de la Membrana Timpánica
/
Modelos Animales de Enfermedad
Límite:
Animals
Idioma:
En
Revista:
Laryngoscope
Asunto de la revista:
OTORRINOLARINGOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Israel
Pais de publicación:
Estados Unidos