Melanin precursors prevent premature age-related and noise-induced hearing loss in albino mice

Abstract

SummaryStrial melanocytes are required for normal development and correct functioning of the cochlea. Hearing deficits have been reported in albino individuals from different species, although melanin appears to be not essential for normal auditory function. We have analyzed the auditory brainstem responses (ABR) of two transgenic mice: YRT2, carrying the entire mouse tyrosinase (Tyr) gene expression-domain and undistinguishable from wild-type pigmented animals; and TyrTH, non-pigmented but ectopically expressing tyrosine hydroxylase (Th) in melanocytes, which generate the precursor metabolite, L-DOPA, but not melanin. We show that young albino mice present a higher prevalence of profound sensorineural deafness and a poorer recovery of auditory thresholds after noise-exposure than transgenic mice. Hearing loss was associated with absence of cochlear melanin or its precursor metabolites and latencies of the central auditory pathway were unaltered. In summary, albino mice show impaired hearing responses during ageing and after noise damage when compared to YRT2 and TyrTH transgenic mice, which do not show the albino-associated ABR alterations. These results demonstrate that melanin precursors, such as L-DOPA, have a protective role in the mammalian cochlea in age-related and noise-induced hearing loss. SignificanceThis manuscript describes how melanin precursors, such as L-DOPA, prevent the profound premature age-related deafness and noise-induced hearing loss associated with albinism in mice. We use two welldefined transgenic mouse models of oculocutaneous albinism type I to study the auditory deficits associated with albinism in mice. We show that melanin and L-DOPA can prevent these hearing alterations. Since L-DOPA alone, a melanin precursor, is enough to rescue the observed deficits we conclude that melanin precursors produced by melanocytes is all what is needed to restore the alterations observed in albino mice by ABR. We do not know the exact mechanism nor we have determined the cause of the hearing loss in these albino mice. However, since melanin (and L-DOPA) can bind calcium we propose that the observed hearing loss phenotype might be caused by alterations in the calcium homeostasis of the endolymph, produced by the stria vascularis of the cochlea, where melanocytes are located within the inner ear. Our work might also be relevant for the corresponding genetic disorder in humans, where, to date, no systematic studies regarding auditory function have been carried out.

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

“…The mysterious and intriguing connection between albinism, light-colored eyes, and deafness is well known many years ago, as Charles Darwin in his 1859 treatise "On the Origin of Species, " wrote that "cats which are entirely white and have blue eyes are generally deaf. " A partial comprehensive view of that connection is quite recent [58] although still uncompleted.…”

“…Supporting that function of cochlear melanin, in humans, hypopigmentation and deafness occur together in the rare Waardenburg syndrome [180]. The absence of melanocytes in the stria vascularis of the inner ear results in cochlear impairment, although the mechanisms for that effect are not well understood [58].…”

Association of Skin Color, Race/Ethnicity, and Hearing Loss Among Adults in the USA

“…The melanin produced by strial melanocytes (intermediate cells) in the cochlea has been hypothesized to serve a protective role as a free radical scavenger, metal chelator, or regulator of calcium homeostasis in the stria vascularis, which is involved with generating and maintaining the endolymphatic potential necessary for normal hearing (Riley 1997;Murillo-Cuesta et al 2010). A recent study has also demonstrated that deficiency in strial melanin is associated with marginal cell loss and decline in the endocochlear potential (Ohlemiller et al 2009a).…”

Natural melanin pigments and their interfaces with metal ions and oxides: emerging concepts and technologies

“…[1] Humans lacking melanocytes (melanin-producing cells) in the ear and animals with albinism (a deficit or absence of melanin) display hearing conditions as in domestic cats with white fur and blue eyes, thus suggesting a biofunctional role of melanin beyond photoprotection. [2,3] In the melanin biopigments family, eumelanin is a brownblack type found in the human body, other mammals, reptiles, amphibians, and fishes as well as in invertebrates, such as cuttlefish and insects; Sepia melanin is a type of natural eumelanin extracted from the ink sac of cuttlefish. Pheomelanin is a yellowish-red melanin.…”