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T. Maeda, A. Maeda, M. Motosky, S. Satsumi Roos, J. Tang, K. Palczewski; Pharmacologic Treatments of a Mouse Model of Age-Related Macular Degeneration Caused by All-Trans-Retinal Clearance Delay. Invest. Ophthalmol. Vis. Sci. 2009;50(13):780.
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To evaluate the efficacy and safety of current potential medications for age-related macular degeneration (AMD) in a mouse model.
Pharmacologic treatments including anti-oxidative agents (ascorbic acid, -lipoic acid, -tocopherol, MnTBAP and butylated hydroxytoluene), immunosuppressant (rapamycin; also has anti-VEGF effects), retinoid cycle inhibitor (retinylamine), artificial chromophore, 9-cis-retinyl acetate (9-cis-R-Ac) were conducted for a mouse model of AMD caused by all-trans-retinal clearance delay with lacks of ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8).
All of the medications partially improved atrophic changes of Rdh8-/-Abca4-/- retina, and retinylamine expressed the best treatment effects among them. Significant reduction of complement deposition at Bruch’s membrane was observed in rapamycin-treated mice, even through severity of retinal degeneration was similar to anti-oxidants and 9-cis-R-Ac treated mice. Rapamycin treatment to 6 months old Rdh8-/-Abca4-/- mice for 4 months prevented the growth of CNV without any change of VEGF level.
Mechanism based therapy with retinylamine demonstrated the best treatment effects on Rdh8-/-Abca4-/- mice, and understanding of fundamental problems in AMD is required to develop effective therapies.
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