C Romano1, M Price, H Y Bai, J W Olney. 1. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110.
Abstract
PURPOSE: This study examined the neuroprotective properties of Honghua, an extract of safflower used as an herbal medicine in China, in several experimental models of retinal ischemia. METHODS: Honghua and other agents were tested (1) in the ex vivo chick embryo retina assay (CER) for anti-excitotoxin efficacy and against simulated ischemia (30 min glucose/oxygen deprivation); and (2) in the in vivo adult rat retina dye-photothrombosis assay. Active components of Honghua were purified by conventional chromatographic techniques. RESULTS: In the CER, Honghua protected against excitotoxicity of glutamate, N-methyl-D-aspartate, kainate, and quisqualate, and against neuronal degeneration caused by simulated ischemia. Honghua more potently protected against simulated ischemia than against the agonists. In the in vivo adult rat retina, ischemic damage was reduced greatly by intravitreal injection of Honghua. An approximately 100-fold purification of an active principle was achieved chromatographically. The purest fractions were rich in glucose, so the effects of glucose in the ischemia models were determined. Many neuroprotective effects of Honghua were mimicked by pure solutions of equivalent glucose concentration. Glucose (> 3.2 mmol/l) in the CER-ischemia assay provided protection. Glucose did not protect against the lesions induced by direct application of the excitotoxic agonists. Intravitreal injection of glucose provided highly significant neuroprotection in the adult rat retina dye-photothrombosis model. CONCLUSIONS: These results suggest that retinal excitotoxic damage in vivo can occur secondary to depletion of cellular energy reserves, and therefore may be prevented by simple procedures that maintain the availability of energy sources.
PURPOSE: This study examined the neuroprotective properties of Honghua, an extract of safflower used as an herbal medicine in China, in several experimental models of retinal ischemia. METHODS: Honghua and other agents were tested (1) in the ex vivo chick embryo retina assay (CER) for anti-excitotoxin efficacy and against simulated ischemia (30 min glucose/oxygen deprivation); and (2) in the in vivo adult rat retina dye-photothrombosis assay. Active components of Honghua were purified by conventional chromatographic techniques. RESULTS: In the CER, Honghua protected against excitotoxicity of glutamate, N-methyl-D-aspartate, kainate, and quisqualate, and against neuronal degeneration caused by simulated ischemia. Honghua more potently protected against simulated ischemia than against the agonists. In the in vivo adult rat retina, ischemic damage was reduced greatly by intravitreal injection of Honghua. An approximately 100-fold purification of an active principle was achieved chromatographically. The purest fractions were rich in glucose, so the effects of glucose in the ischemia models were determined. Many neuroprotective effects of Honghua were mimicked by pure solutions of equivalent glucose concentration. Glucose (> 3.2 mmol/l) in the CER-ischemia assay provided protection. Glucose did not protect against the lesions induced by direct application of the excitotoxic agonists. Intravitreal injection of glucose provided highly significant neuroprotection in the adult rat retina dye-photothrombosis model. CONCLUSIONS: These results suggest that retinal excitotoxic damage in vivo can occur secondary to depletion of cellular energy reserves, and therefore may be prevented by simple procedures that maintain the availability of energy sources.
Authors: Jie Li; Kathleen M Ward; Donglan Zhang; Eswarkumar Dayanandam; Albert S Denittis; George C Prendergast; Iraimoudi S Ayene Journal: Toxicol In Vitro Date: 2012-08-16 Impact factor: 3.500