DISCUSSION
It was found in this study that the retina of BN rat was easily damaged by high doses of NaIO3, from neural retina layers to photoreceptor and RPE cell layers, which was not reversible (Figure 1C). From morphological data we could also note that 60mg/kg NaIO3 induced every severe retina toxicity. In lower doses, such as 20mg/kg NaIO3 or lower, not so much histology changes were found. Even though the functional decrease was observed at the beginning, which could be recovered later. So neither too high nor too low doses of NaIO3 could be suitable for the treatment of dryAMD animal model. Accordingly, 30mg/kg to 40mg/kg NaIO3 would be optimal to be used in this animal model. As far as action mechanism is concerned, larger doses of NaIO3 could destroy all layers of retina whereas lower doses only influence photoreceptors and RPE cells (Figure 3C). Only 30mg/L NaIO3 and higher concentration could suppress RPE cells(Figure 5) , which might indicate that melanin is important for the toxicity of NaIO3 in RPE cells. Since not much melanin exists in the cell cytoplasm, low dose of NaIO3 has no effect on APRE19 cells growth.
Since hydralazine can cause choroidal vasodilatation and increase choroidal blood flow in the eyes, retina can receive more blood and oxygen. We found that for rats treated with 10g/L hydralazine after NaIO3 injection, the ERG cwave didnt fall as markedly as in NaIO3 group. This action of hydralazine might postpone the development of nonexudative agerelated macular degeneration and could be used to treat nonexudative agerelated macular degeneration in the future.
Figure 2 Ocular fundus and fluorescein angiogram on NaIO3 treated BN rats (略)
A: retinograph of 30mg/kg NaIO3 treated BN rat at day 28; B: fluorescein angiogram of 30mg/kg NaIO3 treated BN rat at day 28; C: retinograph of 40mg/kg NaIO3 treated BN rat at day 7; D: fluorescein angiogram of 40mg/kg NaIO3 treated BN rat at day 7; E: retinograph of 40mg/kg NalO3 treated BN rat at day 8
Figure 3 Histology of retina on NaIO3 treated BN rat eyes (略)
A: 20mg/kg NaIO3 at 28 days;B: 30mg/kg NaIO3 at 28 days;C: 40mg/kg NaIO3 at 14 days
Figure 4 Autofluorescence of RPE cells in flatmount induced by laser and measured with confocal microscope(略)
A:normal RPE cells; B: 30mg/kg NaIO3 at 7 days; C: 40mg/kg NaIO3 at 7 days
Figure 5 ARPE19 cells proliferation rate after 48hour treatment with NaIO3(略)
aP<0.05 ,bP<0.01, vs Control
Figure 6 Effects of hydralazine eyedrops on 35mg/kg NaIO3(略)
induced RPE degeneration in rat eyes aP<0.05,bP<0.01, vs Normal, dP<0.01, vs NaIO3
Acknowledgements The authors are grateful to Prof N.S. Peachey, J. Wu, and M. Yu for invaluable assistance in dcERG equipment assembling and measurement. Supported in party by MacuClear, Inc.
【参考文献】
1 Nilsson SEG, Knave B, Persson HE. Changes in ultrastructure and function of the sheep pigment epithelium and retina induced by sodium iodate. Acta Ophthalmol1977;55(6):10271043
2 Grignolo A, Orzalesi N, Calabria GA. Studies on the fine structure and the rhodopsin cycle of the rabbit retina in experimental degeneration induced by sodium iodate. Exp Eye Res 1966;5:8697
3 Hosoda L,AdachiUsami E,Mizota A,Hanawa T,Kimura T.Early effects of sodium iodate injection on ERG in mice. Acta Ophthalmol(Copenh) 1993;71(5):616622
4 Mizota A, AdachiUsami E. Functional recovery of retina after sodium iodate injection in mice. Vision Res 1997;37(14):18591865
5 Korte GE, Wanderman MC. Distribution of Na+ K+ATPase in regenerating retinal pigment epithelium in the rabbit. A study by electron microscopic cytochemistry. Exp Eye Res 1993;56:219229
6 Baich A, Ziegler M. The effect of sodium iodate and melanin on the formation of glyoxylate. Pigment Cell Res1992;5:394395
7 Sorsby A, Reading HW. Experimental degeneration of the retinaⅪ.The effect of sodium iodate on retinalSH levels. Vision Res 1964;4:511514
8 Sorsby A, Reading HW. Experimental degeneration of the retinaⅦ.The protective action of thiol donors against the retinotoxic effect of sodium iodate. Vision Res1962;2:139148
9 Sen HA,Berkowitz BA,Ando N,de Juan E Jr. In vivo imaging of breakdown of the inner and outer bloodretinal barriers. Invest Ophthalmol Vis Sci 1992;33(13):35073512
10 Flage T, Ringvold A. The retinal pigment epithelium diffusion barrier in the rabbit eye after sodium iodate injection. A light and electron microscopic study using horseradish peroxidase as a tracer. Exp Eye Res 1982;34(6):933940
11 Ashburn FS, Pilkerton AR, Rao NA, Marak GE. The effects of iodate and iodoacetate on the retinal adhesion. Invest Ophthalmol Vis Sci 1980;19(12):14271432
12 Stern WH, Ernest JT, Steinberg RH, Miller SS. Interrelationships between the retinal pigment epithelium and the neurosensory retina. Aust J Ophthalmol 1980;8(4):281288
13 Ohtaka K, Machida S, Ohzeki T, Tanaka M, Kurosaka D, Masuda T, Ishii T. Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodateinjected rats. Curr Eye Res 2006;31(4):347355
14 Obata R, Yanagi Y, Tamaki Y, Hozumi K, Mutoh M, Tanaka Y. Retinal degeneration is delayed by tissue factor pathway inhibitor2 in RCS rats and a sodiumiodateinduced model in rabbits. Eye 2005;19(4):464468
15 AtmacaSonmez P, Li Y, Yamauchi Y, Schanie CL, Ildstad ST, Kaplan HJ, Enzmann V. Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE65 in a mouse model of retinal pigment epithelium damage. Exp Eye Res 2006;83(5):12951302 上一页 [1] [2] [3] |