1.Effects of hydralazine on ocular blood flow and laser-induced choroidal neovascularization
International Eye Science 2008;8(12):2359-2363
·AIM: To investigate the effect of hydralazine on choroidal blood flow in rabbits and laser-induced choroidal neovascularization (CNV) in rats and the effect of hydralazine on tube formation of human umbilical vein endothelial cells (HUVEC).used with raised intraocular pressure (IOP) of the left eye to 40mmHg.Hydralazine (10g/L) eye drops were instilled and ocular blood flow was measured with colored microspheres technique. Male Brown Norway rats were treated with Nd: YAG laser to break Bruch's membrane. Hydralazine (5, 10, 20g/L) eye drops or saline alone was instilled three times a day for 4 weeks after laser treatment. Fluorescein angiography (FA) and choroidal flat mount were used to measure the area of CNV. Tube formation of HUVEC was studied at different concen-trations of hydralazine.hydralazine eye drops enhanced the choroidal blood flow significantly at 30 and 60 minutes after drug instillation. After 4 week of drug treatment, 5, 10 and 20g/L hydralazine eye drops all reduced the CNV formation dramatically measured by fluorescein angiography and choroidal flat mount. When HUVEC was cultured on matrix gel for 48 hours, hydralazine at 3-30mg/L preven-ted the tube formation.vivo and HUVEC tube formation in vitro, and enhanced rabbits' choroidal blood flow after ischemia. It is hoped that hydralazine could be used to treat age-related ma-cular degeneration in the future.
2.Pharmacological therapy in age-related macular degeneration (AMD)
Yan-Hong, ZOU ; George C.Y.CHIOU
International Eye Science 2005;5(1):8-18
· Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals aged over 65 in the United States and other industrialized nations. Till now, we have limited choices of treatment for this kind of disease. Treatment available can be grouped into two major categories: physical and pharmacological therapies. The former received extensive attention with little success whereas the latter attract new attention with great hope of success. The pharmacological therapies indude photodynamic therapy (PDT), steroids, vascular endothelial growth factor (VEGF) inhibitors, extracellular matrix (ECM) modifiers, gene therapy, nutrition supplements, choroidal blood flow facilitators and the like. PDT treatment is the only available effective treatment for certain forms of neovascular AMD. Anecortave acetate,as a synthetic derivative of cortisol, might stabilize vision in patients with predominantly classic subfoveal choroidal neovascularization (CNV) for up to 6mo through subtenon juxtascleral depot application. Intravitreous injection of VEGF aptamer stabilized or improved vision in 87.5% of patients with subfoveal CNV 3mo after treatment. Malfunction of choroidal blood flow is found in early stage of AMD. Elevation of intravascular pressure is the crucial hemodynamic factor in age-related macular degeneration, resulting in a decrease of the blood flow of choriocapillaries. Chain reactions are triggered which lead to retinal pigment epithelium (RPE) degeneration,Bruch's membrane breakdown, CNV formation, AMD and blindness in the end. Therefore, specific drugs that can increase the choroidal blood flow could be very useful to prevent the AMD from developing and worsening. Although most of them are still in the experimental stage,it is hopeful to find a way to treat AMD at the early stage and to prevent the disease to be triggered and developed.
3.Effect of hydroxy groups in natural flavones on ocular blood flow of rabbits and retinal function recovery after ischemia insult in rat eyes
Young-Hyun, PARK ; Xin-Rong, XU ; George C.Y.CHIOU
International Eye Science 2004;4(1):1-6
AIM: To determine the effect of hydroxy (OH) group on the ocular blood flow and retinal function recovery.METHODS: Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes and electroretinography was used to measure the retinal function recovery.RESULTS: Flavones with four free OH groups seemed to produce the optimal effects in ocular blood flow increase and retinal function recovery. When there were 3OH groups (Apigenin), rapid increment in ocular blood flow and retinal function recovery was found. When the number of OH groups was below two (7-Hydroxyfiavone,Chrysin), no effect was observed on the ocular blood flow. The attachment of rutinose group in the fiavone (Diosmin) with two free OH groups and methoxy group did not affect the ocular blood flow or retinal function recovery, but the attachment of glucose group in the fiavone (Luteolin-7-glycoside) with catechol group affected the ocular blood flow one way or the other. The attachment of methoxy group in the fiavone (Acacetin)with two free OH groups affected ocular blood flow and retinal function recovery after ischemic insult.CONCLUSION: Ocular blood flow and retinal function recovery are increased significantly with the increase in the number of OH groups attached in the flavone molecule, with the 7-OH group and the catechol group in the B ring the most efficient to enhance the ocular blood flow and retinal function recovery after ischemic insult.