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TitleSonoretina : BRB opening using sonication
PurposePosterior uveitis can require systemic treatments but their intraocular diffusion can be limited by a moderately opened blood-retina barrier (BRB). Sonication corresponds to the use of ultrasounds (US) to increase the permeability of cell barriers.
Objective: Study the efficacy and safety of sonication in retinal pathology by evaluating different US doses and their effect on the inner BRB permeabilization.
MethodsThe eyes of C57bl6 mice were sonicated at different US doses. Efficacy analyzes consisted in showing transient BRB permeabilization on fluorescein angiography (FA) and OCT performed at different time points. The flatmount of retinas and choroids were stained with anti-IgG antibodies to detect areas of vascular leakage. Tolerance was assessed by fundus photographs, immunohistochemistry on flatmounts of sonicated retinas and choroids to study vessel and RPE architecture (isolectin, anti-ZO1 antibodies), RT-q-PCR to look for increased apoptosis or inflammation markers and ERG to assess retinal function.
ResultsSonication at 0.15 mPa seemed to be the most suitable dose for transient (<24h) internal BRB permeabilization (vascular leaks on FA and anti-IgG labeling) without altering the morphology (fundus, OCT, cell junctions) or function of the retina (ERG, gene expression: RDH5, RPE65, OTX2). Sonication at 0.15mPa did not increase the expression of inflammation (TNF, IL6, CCL2) or apoptosis (BAX, CASPASE 9, APAF1) markers in the retina or choroid. The IgG leak on retinal flat-mounts suggests that drugs of high molecular weight (up to 150 kDa) can cross the BRB.
ConclusionSonication at an appropriate dose provides a non-invasive method to increase the diffusion of systemic drugs to the retina without inducing overt inflammation.
Conflict of interestNo
Authors 1
Last nameORTOLI
Initials of first name(s)M