Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
Inner Ear Disorders: From Molecular Mechanisms to Treatment
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Inner Ear Disorders: From Molecular Mechanisms to Treatment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 6371

Special Issue Editor

Dr. Srdjan Vlajkovic

E-Mail Website
Guest Editor
Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Interests: sensory systems; auditory neuroscience; inner ear diseases; inner ear therapeutics; hearing loss; purinergic signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inner ear disorders, ranging from sensorineural hearing loss and tinnitus to balance disorders, pose significant challenges for treatment. The complex interplay of genetic, metabolic, and environmental factors means that treatments must overcome both biological barriers and technological limitations. Over the past several decades, remarkable progress has been made in treating inner ear disorders, yet many challenges remain. Addressing these challenges requires innovative therapeutic strategies integrating modern biotechnology, personalised medicine, and advanced delivery systems.

Some of the pressing questions are indicated below:

  • What is the optimal strategy for regenerating lost hair cells and restoring the damaged inner ear structures?
  • How can therapeutic agents, whether drugs, gene-editing tools, or regenerative factors, be reliably and safely delivered to the inner ear?
  • Which genetic and molecular targets should be prioritised in developing therapies?
  • How do we address the heterogeneity among patients with inner ear disorders?
  • Can we effectively suppress the inflammatory and oxidative stress responses in the inner ear to prevent further cellular damage?
  • How do we effectively integrate biological regenerative therapies with established prosthetic devices, such as cochlear implants, to improve functional outcomes?
  • What are the long-term implications of emerging therapies, and how do we ensure that new treatments are safe and accessible?

The answers to these questions can transform the treatment of hearing loss, tinnitus, and balance disorders and redefine our understanding of sensory restoration and cellular regeneration in the inner ear. Therefore, we invite investigators to contribute original research articles and review articles addressing the mechanisms of inner ear disease, biomarkers of hearing loss and vestibular disorders, biological restoration of hearing and other advances in diagnosis and therapy of inner ear disorders.

Please note that purely clinical studies fall outside the scope of the journal, but clinical submissions with biomolecular studies are welcome.

Dr. Srdjan Vlajkovic
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hearing loss
  • balance disorders
  • stem cell approaches
  • precision gene therapy
  • molecular reprogramming
  • targeted delivery systems
  • molecular biomarkers
  • suppression of oxidative stress and inflammation
  • tissue engineering
  • immune response and off-target effects

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

23 pages, 3158 KB  
Article
Pirfenidone Reduces Intracochlear Fibrosis Caused by Cochlear Implantation in a Guinea Pig Model
by Kady J. Braack, Kelly L. Short, Jorjina Plester, Tylah Miles, Lee Yong Lim, Marcus D. Atlas, Jafri Kuthubutheen, Wilhelmina H. A. M. Mulders and Cecilia M. Prêle
Int. J. Mol. Sci. 2026, 27(7), 3242; https://doi.org/10.3390/ijms27073242 - 2 Apr 2026
Viewed by 578
Abstract
While cochlear implants allow restoration of sound perception in individuals with severe to profound hearing loss, there remains significant variability in patient outcomes. A potential factor that may account for this unexplained variability is the formation of fibrosis within the cochlea after implantation. [...] Read more.
While cochlear implants allow restoration of sound perception in individuals with severe to profound hearing loss, there remains significant variability in patient outcomes. A potential factor that may account for this unexplained variability is the formation of fibrosis within the cochlea after implantation. This study investigated the therapeutic potential of pirfenidone (PFD) in preventing cochlear implant-induced fibrosis and compared outcomes with dexamethasone (DEX) treated animals. The utility of PFD was determined in cultures of fibrocytes isolated from the inner ear of guinea pigs. Specifically, PFD-treatment significantly reduced p38 MAPK signalling, fibrocyte cell proliferation, migration and collagen III deposition in response to pro-fibrotic stimuli. In a guinea pig model, local hydrogel-mediated delivery of PFD to the round window at the time of implant surgery significantly reduced the amount of tissue reaction measured by micro-computed tomography at two months post-implantation (p = 0.0297). Specifically, a 40% decrease in implant-induced tissue reaction was observed in PFD-treated animals compared to vehicle-treated controls. Notably, no evidence of ototoxicity was observed following PFD-treatment. In contrast, a 36% decrease in the amount of tissue reaction was measured in the DEX-treated control group (p = 0.0436). Overall, these data demonstrate that PFD shows significant therapeutic potential in reducing cochlear implant-induced fibrosis. Full article
(This article belongs to the Special Issue Inner Ear Disorders: From Molecular Mechanisms to Treatment)
►▼ Show Figures

Graphical abstract

16 pages, 2852 KB  
Article
Circulating Clues in Ménière’s Disease: Elevated Cell-Free DNA and a Pro-Inflammatory Signature in Patients’ Blood
by Marijana Sekulic, Swethiny Kobivasan, Stavros Giaglis, Daniel Bodmer and Vesna Petkovic
Int. J. Mol. Sci. 2026, 27(4), 1948; https://doi.org/10.3390/ijms27041948 - 18 Feb 2026
Viewed by 616
Abstract
Ménière’s disease (MD) is thought to involve dysfunction of the blood–labyrinth barrier, but circulating mechanisms of endothelial injury remain poorly understood. The present study investigated whether cell-free DNA (cfDNA) and inflammatory mediators in plasma contribute to vascular stress and barrier disruption in MD. [...] Read more.
Ménière’s disease (MD) is thought to involve dysfunction of the blood–labyrinth barrier, but circulating mechanisms of endothelial injury remain poorly understood. The present study investigated whether cell-free DNA (cfDNA) and inflammatory mediators in plasma contribute to vascular stress and barrier disruption in MD. cfDNA levels were significantly elevated in plasma from patients compared with plasma from healthy controls. Exposure of primary human stria vascularis endothelial cell monolayers to plasma from MD patients led to decreased transepithelial electrical resistance and a significant increase in FITC-dextran permeability, indicating impaired barrier function. MD plasma also induced higher lactate dehydrogenase release and pronounced F-actin disorganization with reduced syndecan-1 expression, consistent with endothelial cytotoxicity and glycocalyx degradation. DNase I partially reversed these effects, implicating extracellular DNA as a key driver. Furthermore, IL-1β, CCL3 (MIP-1α), and CCL27 were elevated in MD plasma. Collectively, our data support a model in which cfDNA and inflammatory mediators cooperatively induce endothelial injury, cytoskeletal remodeling, and glycocalyx shedding, leading to blood–labyrinth barrier weakening. Targeting extracellular DNA or glycocalyx preservation may represent a novel strategy to protect inner ear vascular integrity and modify disease progression in MD, and cfDNA-related readouts may be promising biomarkers of endothelial damage. Full article
(This article belongs to the Special Issue Inner Ear Disorders: From Molecular Mechanisms to Treatment)
►▼ Show Figures

Figure 1

Review

Jump to: Research

22 pages, 1040 KB  
Review
Targeting Autophagy for Otoprotection: Translating Basic Mechanisms into Clinical Strategies
by Fei Wang, Tiantian Zhang, Bin Bai, Lian Hui, Yan Wang and Jian Zang
Int. J. Mol. Sci. 2026, 27(5), 2229; https://doi.org/10.3390/ijms27052229 - 27 Feb 2026
Viewed by 472
Abstract
Sensorineural hearing loss (SNHL), the predominant form of global hearing impairment, stems from the irreversible loss of inner ear sensory cells and neurons. Since mammalian cochlea lacks regenerative capacity, cell death represents a final common pathway for diverse insults. Current therapies are merely [...] Read more.
Sensorineural hearing loss (SNHL), the predominant form of global hearing impairment, stems from the irreversible loss of inner ear sensory cells and neurons. Since mammalian cochlea lacks regenerative capacity, cell death represents a final common pathway for diverse insults. Current therapies are merely compensatory, underscoring an urgent need for mechanistic, targeted interventions. Autophagy, a critical homeostatic process, plays complex and dynamic roles in the cochleae. This review synthesizes current evidence on its regulation, highlighting its stage-specific and dual roles in SNHL. We emphasize mitophagy and its context-dependent effects on cell survival. Critically, we discuss an emerging therapeutic paradigm: a dual-phase autophagy modulation strategy. This approach proposes enhancing cytoprotective autophagy in early stages to maintain homeostasis, while inhibiting excessive autophagic flux later to prevent catastrophic cell death. This precision-targeting framework holds significant promise for guiding novel drug development and future clinical translation, moving beyond symptomatic management towards transformative treatment. Full article
(This article belongs to the Special Issue Inner Ear Disorders: From Molecular Mechanisms to Treatment)
►▼ Show Figures

Figure 1

18 pages, 1436 KB  
Review
GJB2-Related Hearing Loss: Genotype-Phenotype Correlations, Natural History, and Emerging Therapeutic Strategies
by Julia Anne Morris, Tomas Gonzalez, Susan H. Blanton, Simon Ignacio Angeli and Xue Zhong Liu
Int. J. Mol. Sci. 2026, 27(1), 491; https://doi.org/10.3390/ijms27010491 - 3 Jan 2026
Viewed by 2555
Abstract
This review integrates molecular, clinical, and translational data to provide an updated understanding of GJB2-related deafness and its emerging treatment landscape. Truncating mutations in GJB2 typically cause severe-profound hearing loss (HL) phenotypes, whereas non-truncating alleles are often associated with milder or progressive [...] Read more.
This review integrates molecular, clinical, and translational data to provide an updated understanding of GJB2-related deafness and its emerging treatment landscape. Truncating mutations in GJB2 typically cause severe-profound hearing loss (HL) phenotypes, whereas non-truncating alleles are often associated with milder or progressive phenotypes. Geographic variation in variant prevalence contributes to regional differences in disease burden. Beyond the coding region, deletions and cis-regulatory mutations within the DFNB1 locus, including GJB6 and CRYL1, can influence HL severity when compounded with other pathogenic GJB2 variants. DFNB1 hearing loss generally presents as symmetric, bilateral, and flat to gently sloping across frequencies, with preserved cochlear neurons that support excellent cochlear implant (CI) outcomes. Early implantation CI in GJB2-positive children yields superior speech and language development compared with non-GJB2 etiologies. Emerging therapies include dual-AAV (AAV1 + AAV-ie/ScPro) delivery, achieving cell-specific Cx26 restoration, adenine base-editing for dominant-negative variants, and allele-specific suppression using RNA interference or antisense oligonucleotides. Concurrent progress in human iPSC-derived cochlear organoids provides a physiologic model to advance toward clinical trials. By integrating genotype-phenotype correlations, natural history insights, and advances in molecular therapeutics, this review presents a comprehensive update on GJB2-related HL and highlights how gene-based strategies are poised to change the treatment of this condition. Full article
(This article belongs to the Special Issue Inner Ear Disorders: From Molecular Mechanisms to Treatment)
►▼ Show Figures

Figure 1

24 pages, 4537 KB  
Review
Cochlear Homeostasis in Sensorineural Hearing Loss: Mechanisms, Implications, and Therapeutic Prospects
by Srdjan M. Vlajkovic, Haruna Suzuki-Kerr and Bryony A. Nayagam
Int. J. Mol. Sci. 2026, 27(1), 102; https://doi.org/10.3390/ijms27010102 - 22 Dec 2025
Cited by 1 | Viewed by 1599
Abstract
Cochlear homeostasis is critical for the preservation of hearing sensitivity by maintaining optimal cochlear fluid composition, sustaining electrochemical gradients, and supporting the function of sensory and supporting cells in the cochlea. Sensorineural hearing loss, resulting from the damage or loss of sensory hair [...] Read more.
Cochlear homeostasis is critical for the preservation of hearing sensitivity by maintaining optimal cochlear fluid composition, sustaining electrochemical gradients, and supporting the function of sensory and supporting cells in the cochlea. Sensorineural hearing loss, resulting from the damage or loss of sensory hair cells, auditory neurons and other cochlear cells and structures, is intimately linked to disruptions in the homeostatic environment. In this narrative review, we explore the cellular and molecular pathways underpinning cochlear homeostasis in health and disease and examine the mechanisms by which failed homeostasis leads to sensorineural hearing loss. We further discuss current research avenues and emerging therapeutic strategies to restore or compensate for the loss of homeostatic balance. These interventions suggest a future where regenerative healing is possible, ultimately leading to permanent repair and functional recovery. Full article
(This article belongs to the Special Issue Inner Ear Disorders: From Molecular Mechanisms to Treatment)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop