Abstract
AimTo evaluate the feasibility of microRNAs (miR) in clinical use to fill in the gap of current methodology commonly used to test hearing impairment in MELAS patients.Material and methodA literature review was performed using the following keywords, i.e., MELAS, Hearing Loss, Hearing Impairment, Temporal Bone, Otoacustic Emission (OTOAE), Auditory Brain Response (ABR), and microRNA. We reviewed the literature and focused on the aspect of the temporal bone, the results of electrophysiological tests in human clinical studies, and the use of miR for detecting lesions in the cochlea in patients with MELAS.ResultsIn patients with MELAS, Spiral Ganglions (SG), stria vascularis (SV), and hair cells are damaged, and these damages affect in different ways various structures of the temporal bone. The function of these cells is typically investigated using OTOAE and ABR, but in patients with MELAS these tests provide inconsistent results, since OTOAE response is absent and ABR is normal. The normal ABR responses are unexpected given the SG loss in the temporal bone.Recent studies in humans and animals have shown that miRs, and in particular miRs 34a, 29b, 76, 96, and 431, can detect damage in the cells of the cochlea with high sensitivity. Studies that focus on the temporal bone aspects have reported that miRs increase is correlated with the death of specific cells of the inner ear.MiR − 9/9* was identified as a biomarker of human brain damage, miRs levels increase might be related to damage in the central auditory pathways and these increased levels could identify the damage with higher sensitivity and several months before than electrophysiological testing.ConclusionWe suggest that due to their accuracy and sensitivity, miRs might help monitor the progression of SNHL in patients with MELAS.
Highlights
MELAS, an acronym for myopathy, encephalopathy, lactic acidosis and stroke like episode syndrome [1], is a mitochondrial disease that can arise from 10 different mitochondrial DNA mutations; in 80% of the cases it is caused by a 3243A > G point mutation in the leucine transfer RNA gene [1, 2]
Temporal bone aspect and mitochondrial alteration in patients with MELAS In patients with MELAS, stria vascularis (SV) displays severe atrophy that affects all turns of the cochlea [10]; the Spiral Ganglions (SG) are reduced in number when compared with SGs in gender- and age-matched healthy subjects [10, 11]
Takahashi et al [10] reported that Organ of Corti showed no alterations, and that inner and outer hair cells were normal in number and function; these findings could be due to the fact that in this study patients were under 30 years old; other MELAS temporal bone studies descriptions are scarce
Summary
MELAS, an acronym for myopathy, encephalopathy, lactic acidosis and stroke like episode syndrome [1], is a mitochondrial disease that can arise from 10 different mitochondrial DNA (mtDNA) mutations; in 80% of the cases it is caused by a 3243A > G point mutation in the leucine transfer RNA gene [1, 2]. Schucknect and Gacek described four forms of Sensorineural Hearing Loss (SNHL) [7, 8], namely: 1) Sensory when hair cells are the most affected; this SNHL form is characterized by a down-sloping audiogram (Fig. 1a); 2) Neural when SGs are the most damaged structures; this SNHL form is characterized by a stable pure tone threshold and a progressive loss of word discrimination (Fig. 1b); 3) Metabolic when SV is the most affected structure; this SNHL form shows a flat or slightly descending pure-tone threshold with good word discrimination (Fig. 1c); and 4) Cochlear Conductive when structures different from the ones described in the other three forms are the origin of SNHL; this SNHL form is characterized by a gentle down-sloping threshold [6–8]. Neural and metabolic forms of SNHL (and their typical auditory thresholds) can be caused by a mitochondrial disease, since mitochondria are present in all types of inner ear cells, they are not homogeneously distributed due to the stochastic segregation; the conductive form cannot be symptom of MELAS because the structure prevalently affected is the middle ear- bone part-
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