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Andre Liber, Rafael Ferraro, Dora Ventura, Francisco Max Damico, Christina Joselevitch; MORPHOLOGICAL STUDY OF THE GANGLION CELL LAYER OF RABBITS AFTER INTRAVITREAL INJECTION OF MYCOPHENOLIC ACID. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3291.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of different concentrations of mycophenolic acid (MPA) injected in the vitreous of New Zealand albino rabbits.
Rabbits were anesthetized with ketamine 10% and xylazine 2%. Intravitreal injections were performed after paracentesis. Right eyes were injected with 1 or 10 mg MPA, and left eyes were injected with 0.1 mL of vehicle (polysorbate 80). After 30 days, animal were sacrificed by intravenous injection of sodium pentobarbital (70 mg/kg). After enucleation, retinas were isolated and fixed in 10% formalin for 48 h and kept in 4% formalin. Isolated retinas were flattened on gelatinized slides and processed for Nissl staining using cresyl violet as dye. Sample retinal fields were photographed throughout the retina at 1 mm intervals with a digital camera attached to a microscope. Neurons in the ganglion cell layer (GCL) within each field were counted using NIH Scion Image 2.0 software. The average density of cells was estimated for each retina along the nasotemporal and dorsoventral axes and the data from each group were compared with those of the corresponding control.
Cell density values along the dorsoventral and nasotemporal axes in the eyes injected with MPA did not differ from those injected with either salineor vehicle. Highest mean densities (±SD) in the dorsoventral axis were 4,094±1,856 (saline), 4,396±1,899 (vehicle), 2,901+1,030 (MPA 1 mg) and 5,156 cells/mm2 (MPA 10 mg), and those in the nasotemporal axis were 2,646±2,085 (saline), 3,612±2,044 (vehicle), 2,678±1,329 (MPA 1 mg) and 3,145±1,709 cells/mm2 in the nasotemporal axis. All values are very close to those reported in literature for albino rabbits.
MPA at 1 and 10 mg does not cause significant decrease in GCL density in New Zealand albino rabbits 30 days after intravitreal injection. Our results suggest multiple interpretations: (a) the doses of MPA used are safe to the retina, (b) the GCL recovers by day 30 post intravitreal injection, (c) damage starts more than 30 days after treatment, or (d) the method used is not sensitive enough to measure retinal toxicity.
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