Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 51, Issue 3, Pages 1747-1754Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.09-4450
Keywords
-
Categories
Funding
- National Eye Institute [EY-017971, P30 EY014801]
- NINDS [NS-061348]
- Hope for Vision and the Seigal Foundation
- Research to Prevent Blindness (University of Miami)
Ask authors/readers for more resources
PURPOSE. Retinal ganglion cells (RGCs) die in glaucoma and virtually all optic neuropathies. Recently, novel tropomyosin-related kinase B (TrkB) monoclonal antibodies have been shown to activate TrkB receptors and exert neuroprotective and neurotrophic effects. In the present study, the authors examined the ability of one of them, 29D7, to elicit RGC survival and neurite growth both in culture and in vivo. METHODS. RGCs from postnatal day (P) 3 to P4 Sprague-Dawley rats were isolated by sequential immunopanning using a monoclonal antibody to Thy1. RGCs were cultured in serum-free defined medium in 96-well plates. RGC viability was assessed after 1 to 3 days by MTT assay. Activation of TrkB and downstream signaling molecules was confirmed by Western blot analysis. Intravitreal injections of 29D7 were performed after optic nerve axotomy, and subsequent RGC survival was quantified using beta-III tubulin immunostaining. Regeneration was assessed using retrograde fluorogold tracing in an optic nerve-peripheral nerve graft model. RESULTS. Similar to brain-derived neurotrophic factor (BDNF), the 29D7 antibody strongly promoted RGC survival and neurite growth in vitro compared with medium alone or control IgG. Forskolin, which weakly supported RGC survival on its own, potentiated the effect of 29D7. Intravitreal injection of 29D7 enhanced RGC survival but not regeneration in vivo 2 weeks after optic nerve injury. CONCLUSIONS. Together, these findings demonstrate the potential for antibody-mediated TrkB agonism as a potential therapeutic approach to enhance RGC survival after optic nerve injury. Further studies are needed to elucidate the mechanistic differences between this TrkB agonist and BDNF. (Invest Ophthalmol Vis Sci. 2010;51:1747-1754) DOI:10.1167/iovs.09-4450
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available