Precise lesion of the vestibular organs using photodynamic therapy for vertigo treatment

Abstract

People feel vertigo and dizziness when the vestibular system is dysfunctional. Conventional treatments for persistent, severe vestibular vertigo include surgery (semicircular canal occlusion and vestibular neurectomy) and administration of ototoxic drugs (intratympanic injection of aminoglycoside gentamicin), both of which alleviate (or suppress) vertigo by vestibular lesion. However, surgery is challenged due to its side effects on the cochlear components, and the ototoxic drug is criticized because of its non-specified injury on adjacent cochlea, which would lead to hearing loss. Thus, it is important to establish a novel approach that could precisely target the vestibular organs with minimal damage on hearing. To this end, we utilized the mechanism of photodynamic therapy (PDT) to realize precise injury on the vestibular apparatus, because of its excellent spatial and temporal specificity and minimal invasion to the non-targeted tissues. Here, we designed biodegradable nanoparticles loading with photosensitizer Chlorin e6 as the “drug” that could be excited by 650 nm light for reactive oxygen species generation to damage biological tissues. The lesion was achieved in vitro on HEI-OC1 cells and cochlear explants, and in vivo on mouse vestibular organs without impeding hearing. Furthermore, within the vestibular organ, the lesion can be restricted in the semicircular canal by adjusting the PDT dosage, which is the common treatment location of benign paroxysmal positional vertigo (BPPV) in clinic. The functional effect of PDT in vivo was evaluated by two tests: vestibular-ocular-reflex test for the function of the semicircular canal and off-vertical-axis-rotation test for the function of the utricle. After the PDT damage, the eye movements of the mice significantly decreased in the vestibular functional tests. The results demonstrated the feasibility of PDT to injure single vestibular organ with controllable damage level and location precision. The PDT approach on mouse vestibular apparatus in this study provides technical foundation for potential clinical treatment of vertigo with PDT.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Pingbo HUANG (Supervisor) & Fangyi Chen (Supervisor)