Current and Future Treatment Options for Hearing Loss

Hearing loss is caused by several factors, such as genetic, aging, drug, infection and exposure to loud sound and around 360 million people worldwide have disabling hearing loss. Here, we discuss the current and future strategies for the treatment of hearing loss

Cell Therapy Development in Hearing Loss

Since the potential of stem cells (SCs) in treating diseases is superb, it is believed that the use of SCs is a promising therapeutic approach in hearing damage. More than 250 million people of worldwide are born deaf. The deaf hearing generally originate from defect on sensory receptors (hair cells) or nerves associated with them (spiral ganglion neurons). Hair cells in some animals such as fish, amphibians and birds can regenerate or replace by new cells, but damage to the hair cells in mammals are not being replaced through cell division or regeneration in the inner ear. Cell therapy for hearing loss is still several years away, but researches opens up possibilities for restoring hearing in the future. Here we review developments in cell therapy approach in treatment of hearing loss

Signaling Pathways Involved in Auditory Hair Cells Development

Auditory hair cells (HCs) cannot be spontaneously regenerated or replaced in mammalian damaged cochlea which leads to permanent deafness. On the other hand, regenerative ability of HCs in lower vertebrates such as birds and amphibians causes that researchers investigate underlying mechanisms and pathways which can possibly induce mammalian cochlear HCs regeneration and hearing recovery. Signaling cascades of HCs regeneration in lower vertebrate can be considered as the potential therapeutic option for the hearing loss in human. This paper reviews current knowledge about the main signaling pathways involved in HCs development in the mammalian cochlea

Approaches of auditory hair cells induction from stem cells

Hair cells are the sensory epithelial cells of both the auditory and the vestibular systems in the inner ear of all vertebrates. Auditory hair cells are located in the organ of corti on a thin layer of basement membrane in the cochlea of the inner ear. Damage to hair cells decreases hearing sensitivity. When these delicate hair cells in the cochlea are damaged, sound signals cannot be sent to the brain. In general, damage to the mammalian inner ear, is not returnable. In fact, a key goal in the treatment of sensorineural hearing loss is to find appropriate procedures to replace the missing hair cells. Cell therapy is one of the treatment options for hearing loss. In this regard, studies focus on ways which hair cells can be provided from exogenous and endogenous stem cells. This review identified ways to induce auditory hair cells regeneration from stem cells as the potential therapeutic approaches for the hearing loss

Stem Cells Injected into the Deaf Rat Cochlea via Round Window Could Survive for at Least One Week in the Endolymph

Background: Noise-induced hearing loss (NIHL) is caused by chronic exposure to high-intensity sound. Although noise hazard has been extensively studied in the past decades, cochlear implants and hearing aids are only safe and clinically effective intervention in hearing-impaired person. In recent years, stem cell therapy has been studied to repair damaged inner ear tissue including hair cells and spiral ganglion neurons (SGNs). Because of small size and complex structure of the cochlea, it is difficult to transplant stem cells. It is necessary; stem cell injection procedure has a minimal adverse effect on target tissue. Cochleostomy are currently used to inject stem cells that can impair hearing. In addition, cell viability is an essential factor in the regeneration of damaged hair cells. Aim: The aim of this study was to examine the survival of bone marrow mesenchymal stem cells (BMSCs) injected through the round window of the NIHL rat model. Methods: Adult male rats were exposed to the 110 dB white noise paradigm for 6 hours in 5 days to induce deafness. Distortion-product otoacoustic emission (DPOAE) was recorded before and after noise exposure. Hoechst labeled-cells were transplanted into the rat cochlea through the round window. Hoechst- labelled MSCs were assayed in the endolymph for 24h, 72h, seven and 10 days after injection. Results: Our findings revealed that stem cell transplantation into the cochlea via round window niche is a safe surgical approach. As well, cells transplanted into the endolymph survived for a postoperative period of at least 1 week. Conclusion: BMSC can survive at least one week in adult rat cochlea after injection through the round window niche

Molecular and Cellular Basis of Misfolded Proteins in Neurodegenerative Diseases

Neurodegeneration is characterized by a progressive loss of nerve structure and function which lead to cognitive impairment such as dementia. Neurodegenerative diseases (NDs) are partially caused by neuronal cell death and glial homeostasis. NDs such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) can develop with aging. As well, in Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), genetic mutations can affect CNS cell function. NDs occur through important processes including, protein misfolding and aggregation of misfolded proteins. These processes cause neurofibrillary tangles and plaques that result in neuronal cytotoxicity. Here, our intention is to shed light on some of the key roles of protein misfolding and aggregation in NDs. This review focuses specifically on understanding the molecular and cell-based mechanisms of protein misfolding and aggregation involved in the development of NDs

Ribbon Synapse Reformation: A Key Role for the Hearing Restoration; A Review

Background: Auditory sensory epithelium of mammals has two types of mechanosensory cells including the inner hair cells (IHC) and outer hair cells (OHC). IHC in the mammalian inner ear is an important component for the sound perception. Information about the frequency, intensity, and timingof acoustic signals is transmitted rapidly and precisely via ribbon synapses of the IHCs to the type 1 spiral ganglion neurons (SGNs). Even in the absence of stimulation, these synapses drive spontaneous spiking into the afferent neuron. Evidence has shown that cochlear neuropathy leading to hearing loss may be a result of the damage to ribbon synapses Aim:Here, we review how these synapses promote the rapid neurotransmitter release and sustained signal transmission. We also discuss the mechanisms involved in ribbon synapse reformation for hearing restoration. Conclusion:Although cochlear ribbon synapses fail to regenerate spontaneously when injured, recent studies have provided evidence for cochlear synaptogenesis that will be relevant to regenerative methods for cochlear neural loss. A better understanding of mechanisms underlying synaptic reformation would be helpful in achieving reversal of sensorineural hearing loss

Gene Therapy in Hearing Loss Treatment: A Review

Background Hearing loss, which is highly heterogeneous, is the most common sensorineural disorder in humans. More than 50% of the causes of deafness are attributed to genetic factors. Numerous studies have shown the persistent negative impact of deafness on communication and quality of life. Therefore, action to optimize performance and maintain or improve hearing ability seems necessary. In so doing, interventions are performed after assessing hearing loss. The most important intervention is gene therapy; For several genetic diseases, gene therapy is a potential treatment that is being investigated. Gene therapy will restore the ability to hear by overcoming functional defects caused by genetic mutations. Furthermore, gene therapy might potentially be used to trigger the regeneration of hair cells by transferring genes required in the cochlea for hair cell differentiation. Aim: We review recent research about hereditary hearing loss and technologies in animal. Methods: In this study, we review current reports in clarifying genomics of hereditary hearing loss and technologies between 2014 and 2020 in PubMed, Scopus, and Google Scholar to create a gene therapy that may soon become a treatment choice. We also discuss recent research applied to animal models of hearing loss by gene therapy. Conclusion: Gene therapy allows for the treatment of sensorineural hearing loss by restoring and/or preserving the inner ear cells functioning. Hopeful results from recent research have contributed to cochlear gene therapies being created for end-use in patients

The effects of modern therapies on noise pollution affecting hearing loss: challenges and novelty

Background: Human reactions to noise pollution can have detrimental consequences for physical and mental health. Increased infection in the workplace or the surrounding area can cause deafness and its disorders, tinnitus, high blood pressure, coronary artery disease, and sleep disorders. Changes in the immune system and birth defects have also been attributed to exposure to noise pollution. Adverse effects and cardiovascular complications due to constant exposure to noise pollution prevent human blood pressure from experiencing a regular cycle of increase and decrease around the clock. The most important sources of such pollution are cars, airplanes, long-term exposure to loud music, and industrial noise. In the European Union, more than 10,000 people die each year due to the effects of noise pollution. The level of noise pollution during the night causes the production and permanent increase of cortisol, which increases the risk of heart attack. Aim: The aim of this study was to review the results of research on the role of antioxidants and other protective agents against the destructive effects of free radicals on hearing loss and deafness. Methods: In this research, using the desired keywords in valid databases (PubMed, Scopus, and Medline), articles from 2016 to 2020 were performed and then this study was written by studying the selected articles. Results: The results showed that most of the pollution is caused by cars, airplanes, long-term exposure to loud music and industrial sounds, as well as protection and training methods, as well as the use of neurotrophic agents and antioxidants and cell therapy. Gene therapy is effective in treating deafness caused by infection. Conclusion: The most appropriate method in the treatment of noise pollution and deafness is the prevention of areas with high noise and the use of antioxidants

Trehalose increase proliferation and decrease apoptosis in hair cells induced by Hydrogen peroxides

BACKGROUND: Hydrogen peroxide (H2O2) a key reactive oxygen species, which is made through redox procedure, can induce oxidative damage to several biological macromolecules and play critical role in neurodegenerative diseases. Aim: The current study examined the neuroprotective effect of Trehalose on hair cells death induced by H2O2. Material and method: Hair cells were co-treated by Trehalose and H2O2. The effects of Trehalose on BAX/BCL2 expression ratio and cell viability were assessed by Real time PCR and MTT assay, respectively.  Result:  The results of Real time PCR and MTT assay indicated that H2O2 induce cell death, and Trehalose have neuroprotective effect and decreases cell death. Conclusion: Our data showed that Trehalose has the protective effect on hair cells death induced by H20