Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction

Shibata, Seiji; Osumi, Yasunori; Yagi, Minoru; Kanda, Seiji; Kawamoto, Kohei; Kuriyama, Hiromichi; Nishiyama, Toshimasa; Yamashita, Toshio

doi:10.1016/j.brainres.2007.01.090

Cited by 23 publications

(11 citation statements)

References 55 publications

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“…The presence of GDNF and GFRα-1 in human corneal and limbal epithelial tissues was confirmed by western blot analysis (fig 2). The reported molecular weight of GDNF is 21 kDa 15 and its glycosylated, disulfide-bonded homodimer protein has been noted to be about 35 kDa 16. A 35 kDa band of glycosylated GDNF was detected in both the limbal and the corneal epithelia, while the 21 kDa band was only detected in the limbal epithelium.…”

Section: Resultsmentioning

confidence: 99%

Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium

Bian

et al. 2008

British Journal of Ophthalmology

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Aim-To evaluate the expression pattern of glial cell line-derived neurotrophic factor (GDNF) with its receptors GDNF family receptor alpha-1 (GFRα-1) and Ret in the human corneal and limbal tissues, as well as in the primary human limbal epithelial cultures (PHLEC).Methods-Expression of GDNF and its receptors, and the co-localisation with stem cell associated and differentiation markers were evaluated by immunofluorescent staining, western blot analysis and real-time PCR in the fresh human corneoscleral tissues, as well as in the PHLEC. Single cell colony-forming and wound-healing assays were also evaluated in PHLEC.Results-GDNF and GFRα-1 were found to be expressed by a subset of basal cells and colocalised with ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2) and p63, but not with cytokeratin 3 in the human limbal basal epithelium. In PHLEC, they were expressed by a small population of cells in the less differentiated stage. The GDNF and GFRα-1-positive subpopulations were enriched for the expression of ABCG2 and p63 (p<0.01). Recombinant human GDNF promoted the proliferation and wound healing of epithelial cells in the PHLEC. In contrast, Ret was abundantly located in the human corneal epithelium except for the basal cells of the limbal epithelium.Conclusion-These findings indicate that GDNF and GFRα-1 may represent a property for the phenotype of human corneal epithelial precursor cells. GDNF may signal independently of Ret through GFRα-1 in the stem cell-containing limbal epithelium.Glial cell line-derived neurotrophic factor (GDNF) is a member of the GDNF family of neurotrophic factors, which also includes neurturin, artemin and persephin. 1 GDNF exerts its effects through a multicomponent receptor system consisting of the GDNF family receptor alpha-1 (GFRα-1), Ret receptor tyrosine kinase (Ret) and neural cell adhesion molecule (NCAM).2 3 GDNF has been shown to support the growth, maintenance and differentiation of a wide variety of neuronal systems. In recent years, GDNF was identified as an essential growth factor maintaining mouse spermatogonial stem cells,4 and it was found to increase motility and survival of cultured mesenchymal stem cells and ameliorate Corneal epithelial homeostasis is governed by a small subpopulation of corneal epithelial SCs located in the basal layer of the limbus.6 -8 However, no direct method has been found to identify the corneal epithelial SCs to date because of the lack of a unique molecular marker. In recent years, the functional role and the possible signal-transduction pathways induced by GDNF in the corneal epithelium have been investigated.9 10 GDNF may play an important role in corneal regeneration and wound healing. In the present study, we evaluated the expression pattern of GDNF with its receptors in the human corneal and limbal epithelia, as well as in the primary limbal epithelial cell cultures (PHLEC), with the intention of exploring the potential role of GDNF in the human stem cell niche. MATERIALS AND METHODS Materials and reagentsProgenit...

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Section: Resultsmentioning

confidence: 99%

Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium

Bian

et al. 2008

British Journal of Ophthalmology

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“…Another successful line of protection utilized neurotrophins but the efficacy of neurotrophic factors varied with the individual compound and the dose administered 65–68 . Direct injection of glial cell line-derived neurotrophic factor (GDNF) into the guinea pig cochlea provided protection in a dose-dependent manner, although the highest doses of GDNF actually increased susceptibility to noise 65 .…”

Section: Pharmaceutical Intervention In Animal Modelsmentioning

confidence: 99%

Emerging therapeutic interventions against noise-induced hearing loss

Sha

Schacht

2016

Expert Opinion on Investigational Drugs

106

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Introduction Noise-induced hearing loss (NIHL) due to industrial, military, and recreational noise exposure is a major, but also potentially preventable cause of acquired hearing loss. For the United States it is estimated that 26 million people (15% of the population) between the ages of 20 and 69 have a high-frequency NIHL at a detriment to the quality of life of the affected individuals and great economic cost to society. Areas covered This review outlines the pathology and pathophysiology of hearing loss as seen in humans and animal models. Results from molecular studies are presented that have provided the basis for therapeutic strategies successfully applied to animals. Several compounds emerging from these studies (mostly antioxidants) are now being tested in field trials. Expert opinion Although no clinically applicable intervention has been approved yet, recent trials are encouraging. In order to maximize protective therapies, future work needs to apply stringent criteria for noise exposure and outcome parameters. Attention needs to be paid not only to permanent NIHL due to death of sensory cells but also to temporary effects that may show delayed consequences. Existing results combined with the search for efficacious new therapies should establish a viable treatment within a decade.

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“…Another line of protection has successfully utilized neurotrophins, though the efficacy of neurotrophic factors varies with the individual compounds and the dose administered [58,59,60,61,62]. Direct injection of glial cell line-derived neurotrophic factor (GDNF) into the guinea pig cochlea provided protection in a dose-dependent manner, although high doses of GDNF actually increased susceptibility to noise [58].…”

Section: Noise-induced Hearing Loss (Nihl) - Backgroundmentioning

confidence: 99%

Emerging treatments for noise-induced hearing loss

Oishi¹,

Schacht²

2011

Expert Opinion on Emerging Drugs

162

118

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Introduction Approximately 5% of the population worldwide suffer from industrial, military, or recreational noise-induced hearing loss (NIHL) at great economic cost and detriment to the quality of life of affected individuals. This review discusses pharmacological strategies to attenuate NIHL that have been developed in animal models and that are now beginning to be tested in field trials. Areas covered The review describes the epidemiology, pathology and pathophysiology of NIHL in experimental animals and human. The underlying molecular mechanisms of damage are then discussed as a basis for therapeutic approaches to ameliorate the loss of auditory function. Finally, studies in military, industrial, and recreational settings are evaluated. Literature was searched employing the terms “noise-induced hearing loss” and “noise trauma”. Expert opinion NIHL, in principle, can be prevented. With the current pace of development, oral drugs to protect against NIHL should be available within the next 5 to 10 years. Positive results from ongoing trials combined with additional laboratory tests might accelerate the time from the bench to clinical treatment.

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Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction

Cited by 23 publications

References 55 publications

Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium

Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium

Emerging therapeutic interventions against noise-induced hearing loss

Emerging treatments for noise-induced hearing loss

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