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Abstract #17562 Published in IGR 9-2
Neuroprotection of retinal ganglion cells in DBA/2J mice with GDNF-loaded biodegradable microspheres
Ward MS; Khoobehi A; Lavik EB; Langer R; Young MJJournal of Pharmaceutical Sciences 2007; 96: 558-568
This study aims to promote long-term retinal ganglion cell (RGC) survival in a spontaneous glaucoma model by injecting slow-release Poly(DL-lactide-co- glycolide) (PLGA) microspheres containing glial cell line-derived neurotrophic factor (GDNF) into the vitreous. Microspheres (1 μL) suspended in PBS were injected in ipsilateral eyes while contralateral eyes served as untreated controls. Mice were injected at two-month intervals (1-4 injections) depending on the protocol. ELISA assay indicated a cumulative GDNF release of 35.4 ng/mg over 71 days. The release was nonlinear with an initial burst of over 50%. Mice displayed a 30% drop in RGC density by eight months (p = 0.013) and 80% drop by ten months (p < 0.01). GDNF delivery increased RGC survival in all groups. Mice receiving early treatment showed up to 3.5 times greater RGC density than untreated mice at 15-months survival (p < 0.05). No significant effect was found in sham or lens injury groups. Microsphere-delivered GDNF significantly increases long-term RGC survival in a spontaneous glaucoma model, although the nonlinear release kinetics suggest that burst release may play a role in this rescue. Neuroprotection with slow-release polymers with improved release kinetics should be further studied as a potential therapy for glaucoma and other diseases involving the loss of central nervous system neurons.
Dr. M.J. Young, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA. mikey@vision.eri.harvard.edu
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)