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T.L. Walraven, R. Buddi, S. Kapi, G.W. Abrams, R. Iezzi; "Chronic Intravitreal Infusion of Phototriggerable Neurotransmitters for Retinal Prosthesis, in vivo." . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4211.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously characterized the toxicological profiles for a number of phototriggerable neurotransmitters, in vitro. The purpose of this study was to develop a chronic, in vivo, intravitreal infusion model in the rat eye to assess the toxicological profiles, anatomical and functional effects of L–glutamate, hPA caged–glutamate and phosphate–buffered saline on the retina. Methods:Six, adult male Sprague–Dawley rats (200–225g) were implanted with Alzet osmotic mini–pumps connected to fine gauge cannulas. Flow through the cannulas was verified prior to transcleral insertion into the vitreous cavity. Cannulas were secured to the eye wall with cyanoacrylate tissue adhesive. The mini–pumps chronically infused phosphate buffered saline (PBS), L–glutamate (5mM), or hPA–caged glutamate (5mM) at a rate of 0.5uL/hr. ERG recordings were performed before and after 1 week of infusion. Optical coherence tomography (OCT) was used to measure retinal thickness before and after 1 week of infusion. Results: Six rats received transcleral infusion cannula implants. Two animals developed cataract in the implanted eye, which prevented OCT analysis. In the remaining four animals, comparisons between pre– and post–infusion OCT retinal thickness revealed no significant differences, throughout the duration of the infusion, regardless of the infusate. Comparisons of retinal thickness between the infused and non–infused fellow eye also revealed no significant differences. Retinal thickness measurements were (PBS pre– 220.0 ± 14.6 uM, post– 211.2 ± 11.8 uM; hPA–glut pre– 204.3 ± 15.1 uM, post– 210.7 ± 12.1 uM; L–glut pre– 207.6 ± 16.4 uM, post– 210.4 ± 11.7 uM). Animals that received L–glutamate infusions demonstrated extinguished ERG a– and b– waves. However, those eyes that received chronic hPA–glutamate infusions did not demonstrate reduced ERG a– and b– wave amplitudes. Conclusion:Chronic transcleral infusion of drugs is feasible using our rat model. Intravitreal infusion of L–glutamate resulted in a loss of ERG a– and b– waves, while hPA glutamate did not appear to affect the physiology of the retinal cells. Future work will include histopathology to examine retinal changes associated with extracellular L–glutamate, hPA caged glutamate and control infusions.
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