| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Glaucoma Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland; and the 2Departments of Pharmacology and Therapeutics and 3Ophthalmology, and Powell Gene Therapy Center, University of Florida, Gainesville, Florida.
PURPOSE. To develop a modified adenoassociated viral (AAV) vector capable of efficient transfection of retinal ganglion cells (RGCs) and to test the hypothesis that use of this vector to express brain-derived neurotrophic factor (BDNF) could be protective in experimental glaucoma.
METHODS. Ninety-three rats received one unilateral, intravitreal injection of either normal saline (n = 30), AAV-BDNF-woodchuck hepatitis posttranscriptional regulatory element (WPRE; n = 30), or AAV-green fluorescent protein (GFP)-WPRE (n = 33). Two weeks later, experimental glaucoma was induced in the injected eye by laser application to the trabecular meshwork. Survival of RGCs was estimated by counting axons in optic nerve cross sections after 4 weeks of glaucoma. Transgene expression was assessed by immunohistochemistry, Western blot analysis, and direct visualization of GFP.
RESULTS. The density of GFP-positive cells in retinal wholemounts was 1,828 ± 299 cells/mm2 (72,273 ± 11,814 cells/retina). Exposure to elevated intraocular pressure was similar in all groups. Four weeks after initial laser treatment, axon loss was 52.3% ± 27.1% in the saline-treated group (n = 25) and 52.3% ± 24.2% in the AAV-GFP-WPRE group (n = 30), but only 32.3% ± 23.0% in the AAV-BDNF-WPRE group (n = 27). Survival in AAV-BDNF-WPRE animals increased markedly and the difference was significant compared with those receiving either AAV-GFP-WPRE (P = 0.002, t-test) or saline (P = 0.006, t-test).
CONCLUSIONS. Overexpression of the BDNF gene protects RGC as estimated by axon counts in a rat glaucoma model, further supporting the potential feasibility of neurotrophic therapy as a complement to the lowering of IOP in the treatment of glaucoma.
This article has been cited by other articles:
|
|
 |
|
  A. J. Weber and C. D. Harman BDNF Preserves the Dendritic Morphology of {alpha} and {beta} Ganglion Cells in the Cat Retina after Optic Nerve Injury Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2456 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Mojumder, D. M. Sherry, and L. J. Frishman Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram J. Physiol., May 15, 2008; 586(10): 2551 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-L. Fu, B. Hu, W. Wu, R. B. Pepinsky, S. Mi, and K.-F. So Blocking LINGO-1 Function Promotes Retinal Ganglion Cell Survival Following Ocular Hypertension and Optic Nerve Transection Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 975 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, H. A. Quigley, M. E. Pease, Y. Yang, J. Qian, D. Valenta, and D. J. Zack Changes in Gene Expression in Experimental Glaucoma and Optic Nerve Transection: The Equilibrium between Protective and Detrimental Mechanisms Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5539 - 5548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Fan, X. Li, and N. G. F. Cooper CaMKII{alpha}B Mediates a Survival Response in Retinal Ganglion Cells Subjected to a Glutamate Stimulus Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3854 - 3863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Greenberg, S. F. Geller, D. V. Schaffer, and J. G. Flannery Targeted Transgene Expression in Muller Glia of Normal and Diseased Retinas Using Lentiviral Vectors Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1844 - 1852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Balasubramanian, P. L. Kaufman, and U.S.-Indo Collaborative Research Workshops Group Research Opportunities in Vision: A Report of the U.S.-Indo Workshops on Collaborative Research Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 1717 - 1735. [Full Text] [PDF]
|
|
|
|
|
|
C. J. Lieven, M. J. Hoegger, C. R. Schlieve, and L. A. Levin Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1477 - 1485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Chauhan, T. L. LeVatte, K. L. Garnier, F. Tremblay, I.-H. Pang, A. F. Clark, and M. L. Archibald Semiquantitative Optic Nerve Grading Scheme for Determining Axonal Loss in Experimental Optic Neuropathy Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 634 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. I. Swanson, C. R. Schlieve, C. J. Lieven, and L. A. Levin Neuroprotective Effect of Sulfhydryl Reduction in a Rat Optic Nerve Crush Model Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3737 - 3741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lambiase, P. Tirassa, A. Micera, L. Aloe, and S. Bonini Pharmacokinetics of Conjunctivally Applied Nerve Growth Factor in the Retina and Optic Nerve of Adult Rats Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3800 - 3806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Quigley Glaucoma: Macrocosm to Microcosm The Friedenwald Lecture Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2663 - 2670. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
