Myringotomy in the Junbo mouse model of chronic otitis media alleviates inflammation and cellular hypoxia.
OBJECTIVE
Ventilation of the chronically inflamed middle ear is a key outcome in functional middle ear surgery. Grommets eliminate middle ear effusion, but there is also evidence that they downregulate inflammation. The reason for this is not understood, but there is little to suggest alteration in eustachian tube ventilatory capacity. Previous work has shown that the Junbo mouse model of chronic otitis media has hypoxic middle ear mucosa and bulla fluid leucocytes. Here we explore whether surgical ventilation may alleviate chronic otitis media through downregulation of hypoxia.


METHODS
Surgical intervention on a mouse model of disease.


METHODS
We established patency of myringotomy incision as 5 days in wild-type mice. We performed unilateral myringotomy on three cohorts of mice: 10 wild-type controls, 12 Junbo mice, and 15 Junbo mice with additional removal of middle ear effusion. A small cohort of these mice were labeled in vivo by intraperitoneal injection of pimonidazole to identify tissue hypoxia. Tissues were assessed for mucoperiosteal thickening and pimonidazole labeling, comparing operated to nonoperated ears.


RESULTS
Ventilation of the inflamed Junbo middle ear revealed significant reduction in inflammatory thickening associated with loss of pimonidazole labeling, suggesting resolution of cellular hypoxia.


CONCLUSIONS
Surgical ventilation may achieve therapeutic effect through alleviation of cellular hypoxia in the chronically inflamed middle ear. Targeted molecular therapy of hypoxia signaling may offer future alternative therapy for chronic otitis media.
UCL Ear Institute, London, United Kingdom; MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, United Kingdom; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Department of Otolaryngology, Barts Health NHS Trust, London, United Kingdom.
Mahmood F
MF
Bhutta
Michael T
MT
Cheeseman
Steve D M
SD
Brown
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008876:Middle Ear Ventilation; D010033:Otitis Media / Q000601:surgery*
Junbo mouse model; Otitis media; grommets; hypoxia; ventilation