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S. D. Grozdanic, H. Kecova, M. M. Harper, M. H. Kuehn, E. B. Lavik, R. H. Kardon; BDNF Mediated Functional and Structural Optic Nerve Protection in Canine Hypertensive Eyes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2522.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate therapeutic effects of chronic brain derived neurotrophic growth factor (BDNF) administration in a canine model of ocular hypertension.
Intraocular pressure (IOP) was elevated for 60 minutes to the level of systolic blood pressure using an anterior chamber canula connected to a saline reservoir. Two hours after induction of ocular hypertension intravitreal injections of sustained release BDNF-PLGA microspheres (with degradation and release kinetics of 2 months) or blank PLGA microspheres were given. The function of the optic nerve was evaluated using pattern electroretinography (pERG). Thickness of the retinal nerve fiber layer (RNFL) was evaluated using optical coherence tomography (OCT).
Four weeks after induction of ocular hypertension, BDNF-PLGA injected eyes had significantly better pERG amplitudes (5.3+0.5 µV; mean+SEM, p=0.0047, ANOVA) when compared to dogs which did not receive any treatment (2.5+0.6 µV; mean+SEM) or received only blank microsphere injection (2.4+0.6 µV; mean+SEM). PERG amplitude for healthy non-operated dogs was 6.2+0.5 µV. OCT analysis in BDNF injected eyes showed significant preservation of the inferior RNFL (97.2+3.4 µm; p=0.005) when compared to hypertensive eyes which did not receive any treatment (80.7+4.9 µm) or received blank microspeheres (81.1+2.1 µm). Inferior RNFL thickness in healthy dogs was 98+2.9 µm. Six months post injection pERG function significantly decreased in BDNF treated eyes and was not significantly different compared to hypertensive non-treated eyes.
Chronic delivery of BDNF for 2 months had a significant protective effect on optic nerve function and structure. However, optic nerve degeneration continued to progress once when BDNF trophic support ceased. Chronic BDNF delivery may be an effective strategy for protection of optic nerve function and structure from ocular hypertension.
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