Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

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.

Hearing Loss, Tinnitus, Hyperacusis, and Diplacusis in Professional Musicians: A Systematic Review

“…Future perspectives in noise-induced HL risk prevention are centered on early diagnosis of hearing impairment in predisposed individuals. On this topic, some authors recently proposed the use of microRNAs for monitoring the hearing damage [ 90 ] because they allow to investigate the hearing pathways from periphery (34a, 29b, 76, 96 and 431) to central auditory area (miR − 9/9 *). MicroRNA are very sensible to the cells metabolic alterations and they are commonly used for monitoring the progression of several disease [ 91 , 92 ]; furthermore, they have shown a high sensitivity in the early identification of inner ear cellular damage [ 93 ] and could play a role in the early diagnosis of hearing damage in individuals that are at risk of HL.…”

Temporal bone histopathology in MELAS syndrome

“…It is the most common maternally inherited mitochondrial disease. Although a number of mutations can cause the syndrome, the majority (80%) are caused by a point mutation of alanine and guanine at 3243 . This particular mutation can be identified in other mitochondrial diseases with hearing loss such as MIDD (Maternally Inherited Diabetes mellitus with Deafness) and Kearns‐Sayre syndrome …”

“…MELAS is a syndrome typified by mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes . Although a number of mutations can cause the syndrome, the majority (80%) are caused by a point mutation of alanine and guanine at 3243 . MELAS syndrome is the most common maternally inherited mitochondrial disease.…”

Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

“…We are in the process of exploring the viability of using different techniques based on microRNAs specific for hair cells and SGs [12,13] for monitoring hearing loss progression. Due to their high sensitivity to detect cells death [9] and altered function [8], microRNAs may provide a valid alternative to traditional ABR test.…”