Long-Term Rescue Of Rat Retinal Ganglion Cells And Visual Function By Aav-Mediated Bdnf Expression After Acute Elevation Of Intraocular Pressure

PURPOSE. To evaluate the ability of increased expression of brain-derived neurotrophic factor (BDNF) using adenoassociated viral (AAV) vector to prevent the loss of rat retinal ganglion cells (RGCs) and visual function after acute elevation of intraocular pressure (IOP).METHODS. AAV vectors (expressing BDNF or GFP) were injected into the vitreous 6 hours after a transient IOP elevation to 130 mm Hg for 45 minutes. Protective effects were evaluated by counting RGCs retrogradely labeled with fluorogold (FG) from the superior colliculus, measuring the amplitude and the latency of the P1 component of the visual evoked potential (VEP), and observing the visual acuity and contrast sensitivity in awake and behaving animals.RESULTS. RGC numbers decreased continuously to 9 weeks after the elevation of IOP. FG-positive RGC loss was significantly decreased in the retinas treated with AAV-BDNF at 3, 6, and 9 weeks after the insult, with corresponding improvements in VEP parameters. Supplementing BDNF protein once to compensate for the slow onset of AAV-mediated gene expression rescued a larger number of RGCs and the parameters of the VEP. Visual acuity and contrast sensitivity were significantly improved in all treated groups, with the largest improvement in the combined-therapy group, and were maintained for up to 70 weeks. The authors further demonstrated that BDNF rescued the RGCs by activating TrkB receptors through both autocrine and paracrine mechanisms.CONCLUSIONS. AAV-mediated BDNF expression in the rat retina achieved a sustained rescue of RGCs and visual function after an acute elevation of IOP. (Invest Ophthalmol Vis Sci. 2012;53:1003-1011) DOI:10.1167/iovs.11-8484