Neuroprotective effect of intravitreal cell-based glucagon-like peptide-1 production in the optic nerve crush model

Purpose: To examine the effect of intraocularly produced glucagon-like peptide-1 (GLP-1) on the survival rate of retinal ganglion cells in an optic nerve crush model. Methods: Forty-one Sprague-Dawley rats were divided into a study group (21 animals) in which 4 beads with 3000 genetically modified cells to produce GLP-1 were intravitreally implanted into the right eye; a saline control group (n = 12) with intravitreal saline injection; and a GLP-1 negative bead control group (n = 8) in which 4 beads with 3000 cells without GLP-1 production were intravitreally implanted. The right optic nerves of all animals were crushed in a standardized manner. After labeling the retinal ganglion cells by injecting 3% fluorogold into the superior colliculus, the animals were sacrificed, and the ganglion cells were counted on retinal flat mounts. Results: The retinal ganglion cell density of the right eyes was significantly higher in the study group (median: 2081 cells/mm(2); range: 1182-2953 cells/mm(2)) than in the GLP-1 bead negative control group (median: 1328 cells/mm(2); range: 1007-2068 cells/mm(2); p = 0.002) and than in the saline control group (median: 1777 cells/mm(2); range: 1000-2405 cells/mm(2); p = 0.07). Correspondingly, the survival rate (ratio of retinal ganglion cell density of right eye/left eye) was significantly higher in the study group (median: 0.72; range: 0.40-1.04) than in the GLP-1 bead negative control group (median: 0.44; range: 0.36-0.68; p = 0.003) and than in the saline control group (median: 0.56; range: 0.36-0.89; p = 0.03). Conclusion: Glucagon-like peptide-1 produced by intravitreally implanted cell beads was associated with a higher survival rate of retinal ganglion cells after an experimental optic nerve crush in rats.