Principles of Calcite Dissolution in Human and Artificial Otoconia

Abstract

Human otoconia provide mechanical stimuli to deflect hair cells of the vestibular sensory epithelium for purposes of detecting linear acceleration and head tilts. During lifetime, the volume and number of otoconia are gradually reduced. In a process of degeneration morphological changes occur. Structural changes in human otoconia are assumed to cause vertigo and balance disorders such as benign paroxysmal positional vertigo (BPPV). The aim of this study was to investigate the main principles of morphological changes in human otoconia in dissolution experiments by exposure to hydrochloric acid, EDTA, demineralized water and completely purified water respectively. For comparison reasons artificial (biomimetic) otoconia (calcite gelatin nanocomposits) and natural calcite were used. Morphological changes were detected in time steps by the use of environmental scanning electron microscopy (ESEM). Under in vitro conditions three main dissolution mechanisms were identified as causing characteristic morphological changes of the specimen under consideration: pH drops in the acidic range, complex formation with calcium ions and changes of ion concentrations in the vicinity of otoconia. Shifts in pH cause a more uniform reduction of otoconia size (isotropic dissolution) whereas complexation reactions and changes of the ionic concentrations within the surrounding medium bring about preferred attacks at specific areas (anisotropic dissolution) of human and artificial otoconia. Owing to successive reduction of material, all the dissolution mechanisms finally produce fragments and remnants of otoconia. It can be assumed that the organic component of otoconia is not significantly attacked under the given conditions. Artificial otoconia serve as a suitable model system mimicking chemical attacks on biogenic specimens. The underlying principles of calcite dissolution under in vitro conditions may play a role in otoconia degeneration processes such as BPPV.

The Role of Oxidative Stress and Inflammatory Mediators in Benign Paroxysmal Positional Vertigo

“…Human otoconia are the sensory detector organs found in the utriculus and sacculus for the detection of linear acceleration and head tilt movements against gravity. They contain more than 90% calcite (crystalized calcium carbonate), and they are the only calcite-based biological structures acting in physiological processes in human beings, whereas other two systems, bone and teeth, contain calcium phosphate [12,13] . Calcium and carbonate levels in the endolymph are critical for normal otoconial function, which is primarily provided by a calcium channel transport system expressed in the inner ear [14] .…”

Protective Effect of Ginkgo Biloba Extract on Gentamicin-Induced Structural Changes of Calcite-Gelatin Composite

“…The limitation of this study was the lack of the classical appearance of biologic otoconia. Compared with the artificial otoconia fabricated by Walther et al [6] or Huang et al [4] , our fabricated artificial otoconia is less sophisticated. This is the first study to evaluate the in vitro protective effect of GBE against GM-induced damage of artificial calcite-gelatin composite.…”

“…Since the discovery of the biomimetic growth of artificial otoconia in gelatin gel matrices (calcite-gelatin nanocomposites), which show the same chemical and structural characteristics as human otoconia, it has become possible to detect morphological changes in greater detail, as described in recent studies [4][5][6] . Aminoglycoside antibiotics have been used for the treatment of gram-negative bacterial infection.…”

“…In the inner ear, systemic aminoglycosides cross the blood-labyrinth barrier (BLB) and can damage cochlear hair cells through several mechanisms such as apoptosis or release of reactive oxygen species (ROS), leading to permanent sensorineural hearing loss [22,23] . GM not only damages the vestibular hair cell but also otoconia [24,6] . Vestibular toxicity can be prevented by ROS scavengers, such as superoxide anions and glutathione [25] .…”

“…Previous studies have suggested that the underlying core of glycosaminoglycan fibrils serves as a framework for calcite deposition during otoconial development [2,3] . Since the discovery of the biomimetic growth of artificial otoconia in gelatin gel matrices (calcite-gelatin nanocomposite), which show the same chemical and structural characteristics as human otoconia, it has become possible to detect morphological changes in greater detail, as described in recent studies [4][5][6] . Gentamicin (GM) is an aminoglycoside antibiotic, which is effective against gram-negative bacterial infection [7] .…”