Brain-derived neurotrophic factor gene delivery to muller glia preserves structure and function of light-damaged photoreceptors.

摘要: PURPOSE. To test the hypothesis that adenovirus (Ad)-mediated gene delivery of brain-derived neurotrophic factor (BDNF) to Muller cells can protect photoreceptors from light-induced retinal degeneration. METHODS. Adult Sprague-Dawley rats received an intraocular injection Ad.BDNF, control Ad containing green fluores- cent protein (GFP) gene, or BDNF recombinant protein. Ani- mals were then exposed 5, 10, 16 days constant light. The effect Ad.BDNF on photoreceptor survival was exam- ined histologically, by measuring outer nuclear layer (ONL) thickness, and functionally, electroretino- graphic (ERG) response. RESULTS. mediated sustained expression bioactive neurotrophin lasted for at least 30 after viral vector administration. glia markedly increased structural integrity light- damaged photoreceptors. For example, 10 expo- sure light, average percentage ONL preservation in superior central retina eyes 71%, compared with 46% a Ad.GFP 15% contralateral eyes. Of importance, retinas had more nuclei than single neuroprotective accompanied ERG response treated CONCLUSIONS. These data provide proof concept transfer into is effective strategy preserving structure function (Invest Ophthalmol Vis Sci. 2005;46:3383-3392)