Panel 3: Recent Advances in Anatomy, Pathology, and Cell Biology in Relation to Otitis Media Pathogenesis

Cayé‐Thomasen, Per; Hermansson, Ann; Hellström, Sten; Kanzaki, Sho; Kerschner, Joseph E.; Lim, David J.; Lin, Jizhen; Mason, Kevin M.; Spratley, Jorge

doi:10.1177/0194599813476257

Cited by 21 publications

(12 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Otitis media is estimated to cost the national healthcare system more than $4 billion annually [30], and in extreme cases can result in long-term speech and learning impairments [38]. Currently, genetic risk factors are poorly understood [29], but the prevalence of pediatric cases is commonly believed to be related to the ongoing maturation of the Eustachian tube [39], which undergoes significant development in the first decade of life. Interestingly, hyperphosphatemia in Fgf mice (which precedes other observed symptoms) first appears at P10 [9].…”

Section: Discussionmentioning

confidence: 99%

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

et al. 2014

View full text Add to dashboard Cite

Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf mice are profoundly deaf. Fgf mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf mice demonstrate dysplastic bulla and ossicles; Fgf mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf mice do not match the auditory phenotype of Kl −/− mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media.

show abstract

Section: Discussionmentioning

confidence: 99%

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…We also created a geneset containing genes that have been associated with OM. This consisted of genes derived from GWAS studies, which were downloaded from the NHGRI website, and a number of candidate genes that have been observed or tested in animal models of OM [ 30 - 33 ].…”

Section: Methodsmentioning

confidence: 99%

The transcriptome of a complete episode of acute otitis media

et al. 2015

View full text Add to dashboard Cite

BackgroundOtitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease.The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control). Two independent samples were generated for each time point and condition, from initiation of infection to resolution. RNA was profiled on Affymetrix mouse 430 2.0 whole-genome microarrays.ResultsApproximately 8% of the sampled transcripts defined the signature of acute NTHi-induced otitis media across time. Hierarchical clustering of signal intensities revealed several temporal gene clusters. Network and pathway enrichment analysis of these clusters identified sets of genes involved in activation of the innate immune response, negative regulation of immune response, changes in epithelial and stromal cell markers, and the recruitment/function of neutrophils and macrophages. We also identified key transcriptional regulators related to events in otitis media, which likely determine the expression of these gene clusters. A list of otitis media susceptibility genes, derived from genome-wide association and candidate gene studies, was significantly enriched during the early induction phase and the middle re-modeling phase of otitis but not in the resolution phase. Our results further indicate that positive versus negative regulation of inflammatory processes occur with highly similar kinetics during otitis media, underscoring the importance of anti-inflammatory responses in controlling pathogenesis.ConclusionsThe results characterize the global gene response during otitis media and identify key signaling and transcription factor networks that control the defense of the middle ear against infection. These networks deserve further attention, as dysregulated immune defense and inflammatory responses may contribute to recurrent or chronic otitis in children.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1475-7) contains supplementary material, which is available to authorized users.

show abstract

“…The etiology of OM is multifactorial and relates to anatomical variations, pathophysiology including the interaction between microbial agents and host immune response, and cell biology of the middle ear cleft (mastoid, middle ear cavity, eustachian tube) and nasopharynx 25,26. Viral upper respiratory tract infections often precede or coincide with episodes of AOM; examples include respiratory syncytial virus, adenovirus, and cytomegalovirus 27.…”

Section: Etiologymentioning

confidence: 99%

Update on otitis media – prevention and treatment

Qureishi¹,

Lu²,

Belfield³

et al. 2014

IDR

105

View full text Add to dashboard Cite

Acute otitis media and otitis media with effusion are common childhood disorders, a source of significant morbidity, and a leading cause of antibiotic prescription in primary health care. Although effective treatments are available, some shortcomings remain, and thus better treatments would be welcome. Recent discoveries within the field of otitis media research relating to its etiology and pathogenesis have led to further investigation aimed at developing novel treatments. This article provides a review of the latest evidence relating to the understanding of acute otitis media and otitis media with effusion, current treatment strategies, their limitations, new areas of research, and novel strategies for treatment.

show abstract

Panel 3: Recent Advances in Anatomy, Pathology, and Cell Biology in Relation to Otitis Media Pathogenesis

Abstract: Over the past 4 years, considerable scientific progress has been made on the pathogenesis of OM, as related to issues of anatomy, pathology, and cell biology. Based on these new achievements and a sustained lack of essential knowledge, suggestions for future research are outlined.

Cited by 21 publications

References 128 publications

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

The transcriptome of a complete episode of acute otitis media

Update on otitis media – prevention and treatment

Contact Info

Product

Resources

About

Panel 3: Recent Advances in Anatomy, Pathology, and Cell Biology in Relation to Otitis Media Pathogenesis

Abstract: Over the past 4 years, considerable scientific progress has been made on the pathogenesis of OM, as related to issues of anatomy, pathology, and cell biology. Based on these new achievements and a sustained lack of essential knowledge, suggestions for future research are outlined.

Cited by 21 publications

References 128 publications

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice

The transcriptome of a complete episode of acute otitis media

Update on otitis media &ndash; prevention and treatment

Contact Info

Product

Resources

About

Update on otitis media – prevention and treatment