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Corine Ghosn, James A Burke; fMRI shows Functional Recovery by Intravitreal Brimonidine Drug Delivery System (Brimo DDS Generation 1) in a Rabbit Model of Retinal Ganglion Cell (RGC) Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6127.
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© ARVO (1962-2015); The Authors (2016-present)
fMRI signals are depressed in the visual cortex of glaucoma patients. Brimonidine, an alpha 2 agonist, prevents retinal damage in several animal models, and when formulated in a biodegradable drug delivery system and dosed intravitreally enhanced visual evoked responses in rabbits with naïve eyes (ARVO 2008). The purpose of this study was to evaluate the fMRI response in the visual cortex (VC) after dosing with brimo DDS in eyes with RGC injury.
RGC injury (20 - 40% loss) was induced bilaterally in 12 rabbits by intravitreal 1 mM NMDA. After 4 weeks, Brimo DDS was dosed unilaterally and placebo DDS in the contralateral eye. Blood oxygenation level dependent (BOLD) levels in fully conscious animals were assessed with a 9.4T imaging spectrometer (BioSpec 94/30USR, Bruker Biospin MRI GmbH) in the VC in response to a visual stimulus paradigm before and 4 weeks after NMDA, as well as 2 weeks and 1, 2 and 4 months after DDS. The stimulus used in these experiments consisted of four green LEDs flashing at 8 Hz. The fMRI data were registered to eliminate artifacts from small head movements using a 2-D affine registration method implemented using the Insight ITK toolkit. All trials from each experiment were averaged, and the averaged data were analyzed to detect activated voxels using an unsupervised one-class support vector machine-based algorithm (Song & Wyrwicz, 2009).
NMDA caused a 25% decrease in magnitude and a 50% decrease in area of the BOLD signal. The BOLD signal significantly recovered (100% magnitude, 75% area) on the hemisphere of the VC corresponding to eyes treated with brimo DDS. This effect lasted through 4 months. Placebo DDS was not effective.
Intravitreal Brimo DDS recovers the loss of visual cortex fMRI signal in eyes with RGC injury.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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