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

Abstract

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. 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. 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). 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.