Gail Ishiyama

Changes in the Tiny Vessels of the Inner Ear’s Balance Organ Reveal Links to Ménière’s Disease

By Gail Ishiyama, M.D.

The integrity and permeability of the blood labyrinthine barrier (BLB) in the inner ear is important to maintain an adequate blood supply and to control the passage of fluids, molecules, and ions. Identifying the cellular and structural components of the BLB is critical to understanding inner ear microvasculature (micro vessels) and designing the efficient delivery of therapeutics across the BLB, potentially to treat hearing and balance disorders such as Ménière’s disease.

(A) Uniformly thick vessels (red) in a vestibular schwannoma utricle with arrows pointing to a wrapping pericyte cell. (B) In a thick vessel from a Ménière’s patient, there is disorganization of the pericyte processes (white arrows) and evidence of …

(A) Uniformly thick vessels (red) in a vestibular schwannoma utricle with arrows pointing to a wrapping pericyte cell. (B) In a thick vessel from a Ménière’s patient, there is disorganization of the pericyte processes (white arrows) and evidence of degeneration of the vascular endothelial cells and thin areas of the vessel wall (green). (C) This zoomed-out image shows constriction in the blood vessels (left arrow).

My team and I used fluorescence microscopy to study the microvasculature in the utricular macula, which detects the body’s linear movement, of patients who had undergone surgery for Ménière’s disease or vestibular schwannoma. As published in Frontiers in Cellular Neuroscience on Oct. 4, 2019, we found a significantly decreased number of junctions, total vessel length, and average vessel length in the microvasculature in Ménière’s disease specimens compared with vestibular schwannoma and control specimens.

The vessels in Ménière’s specimens appeared disorganized with abnormal, uneven, or constricted shapes, atypical branching, and decreased coverage and thinning, leaving vascular endothelial cells (VECs) exposed and unprotected. Our prior research had shown that in Ménière’s disease, VECs are damaged and that they contain oxidative stress markers. Our new study underscores possible mechanisms behind BLB disruption in Ménière’s and the subsequent signs of edema (excess fluid), which disrupts the homeostasis of the hearing and balance structures.

The report indicates that interventions aimed at preventing damage to the microvasculature may help stop the progression of damage to the vestibular system, restoring balance and preventing vertigo spells. It could be that decreasing vessel constriction and BLB leakage will help prevent chronic damage to balance structures; this may help explain how steroids administered to Ménière’s patients provide temporary relief from dizziness symptoms.

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The paper also shows that human inner ear tissue can be used to compare and contrast findings in animal models to design better therapies for vestibular and auditory disorders. We hope that the deeper understanding of the anatomy of the BLB and its changes during disease will enable the development of noninvasive delivery strategies for treating hearing and balance disorders.

Gail Ishiyama, M.D., a 2016 and 2018 Emerging Research Grants recipient, is a clinician-scientist who is a neurology associate professor at UCLA’s David Geffen School of Medicine.

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Accomplishments by ERG Alumni

Gail Ishiyama, M.D., a clinician-scientist who is a neurology associate professor at UCLA’s David Geffen School of Medicine, has been investigating balance disorders for nearly two decades and recently coauthored two studies on the topic.

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