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DISCUSSION
AMD is the leading cause of blindness in the elderly worldwide, affecting 3050 million individuals. It is particularly prevalent in the United States and European countries.
Figure 4Effect of flavone on H2O2induced injury in ARPE19 cells ARPE19 cells were incubated with flavone and H2O2 for 24 hours. n=6 in each group; aP<0.05 and bP<0.01 vs model group.
Figure 5Effect of flavone on NaN3induced injury in ARPE19 cells ARPE19 cells were incubated with flavone and NaN3 for 72 hours. n=6 in each group; aP<0.05 and bP<0.01 vs model group.
Figure 6Effect of flavone on tBHPinduced injury in ARPE19 cells ARPE19 cells were incubated with flavone and tBHP for 12 hours. n=6 in each group; aP<0.05 and bP<0.01 vs model group.
It is generally accepted that the impairment of RPE cell function is an early and crucial event in the molecular pathways leading to clinically relevant AMD[12,13]. RPE serves a variety of metabolic and supportive functions that are of vital importance for retinal photoreceptors, including maintenance of the bloodretinal barrier, participation in the visual cycle, and phagocytic uptake and degradation of constantly shed apical photoreceptor outer segments[14]. The direct toxic effect of NaIO3 on RPE cells with secondary effects on photoreceptors and the choriocapillaries in vivo is well known[15]. The results of this research showed that flavone reversed NaIO3induced injury in RPE by 141% at the end of 4 weeks. This result might indicate that flavone had protective effect against NaIO3 induced RPE degeneration in rat eyes and might slow down the development of AMD.
RPE cells are particularly susceptible to oxidative stress because of high concentration of polyunsaturated fatty acids in the outer segments[16] and exposure to visible light[1720]. Different types of oxidative stress results in different patterns of oxidative damage to proteins in RPE cells and different patterns of loss of viability[21]. In addition to this indirect evidence in support of oxidative stress as a pathogenic factor in AMD, clinical data provide direct validation of the antioxidant approach to AMD treatment. It is a general consensus that oxidative damage plays an important role in pathogenesis of dry AMD[22]. Clearly, antioxidants are needed for dry AMD treatment. In this study, H2O2, NaN3 and tBHP was used as oxidants to induce injuries in RPE cells. The results showed flavone reversed the various oxidants induced injuries in RPE cells. In other words, flavone could prevent the oxidative injury of RPE in AMD.
In conclusion, flavone acts as an antioxidant to protect the RPE from damage by oxidative stress. Thus, flavone might be a promising candidate for the treatment of AMD.
【参考文献】
1 Fine SL, Berger JW, Maguire MG, Ho AC. Agerelated macular degeneration. N Engl J Med2000;342:483492
2 Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of agerelated macular degeneration. Am J Ophthalmol2004;137:486495
3 Kuehn BM. Gene discovery provides clues to cause of agerelated macular degeneration. JAMA2005;293:18411845
4 Klein R. The fiveyear incidence and progression of agerelated maculopathy: the Beaver Dam Eye Study. Ophthalmology1997;104:721
5 Lin B, Chiou GCY. Antioxidant activity of naringenin on various oxidants induced damages in ARPE19 cells and HUVEC. Int J Ophthalmol 2008;8:19631967
6 Steinberg RH. The relationship of the retinal pigment epithelium to photoreceptor outer segments in human retina. In: Zinn KM, Marmor MF, eds. The Retinal Pigment Epithelium.MA: Harvard University Press 1979:3244
7 PandaJonas S. Retinal pigment epithelial cell count, distribution, and correlations in normal human eyes. Am J Ophthalmol1996;121:181189
8 Dorey CK. Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci1989;30:16911699
9 Uwe W, Sabine K, Mathias DB, Hannelore D. Dietary flavones is a potent apoptosis inducer in human colon carcinoma cells. Cancer Res 2000;60:38233831
10 Duthie SJ, Dobson VL. Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Eur J Nutr1999;38:2834
11 Peachey NS, Stanton JB, Marmorstein AD. Noninvasive recording and response characteristics of the rat dcelectroretinogram. Vis Neurosci2002;19:694701
12 Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res2005;80:595606
13 Warburton S, Southwick K, Hardman RM, Secrest AM, Grow RK, Xin H, Woolley AT, Burton GF, Thulin CD. Examining the proteins of functional retinal lipofuscin using analysis as a guide for understanding its origin. Mol Vis2005;11:11221134
14 Strauss O. The retinal pigment epithelium in visual function. Physiol
Rev2005;85:845881
15 Kiuchi K, Yoshizawa K, Shikata N, Moriguchi K, Tsubura A. Morphologic characteristics of retinal degeneration induced by sodium iodate in mice. Curr Eye Res2002;25:373379
16 Flieler SJ, Anderson RE. Chemistry and metabolism of lipids in the vertebrate retina. Prog Lipid Res1983;22:79131
17 Gaillard ER, AthertonEldred G, Dillon J. Photophysical studies on human retinal lipofuscin. Photochem Photobiol1995;61:448453
18 Rzanowska M, Wessels J, Boulton M, Burke JM, Rodgers MA, Truscott TG, Sarna T. Blue lightinduced singlet oxygen generation by retinal lipofuscin in nonpolar media. Free Radic Biol Med1998;24:11071112
19 Sparrow JR, Zhou J, BenShabat S, Vollmer H, Itagaki Y, Nakanishi K. Involvement of oxidative mechanisms in bluelightinduced damage to A2Eladen RPE. Invest Ophthalmol Vis Sci2002;43:12221227
20 Sparrow JR, VollmerSnarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, Nakanishi K. A2Eepoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2Eepoxide formation. J Biol Chem2003;278:1820718213
21 Chiou GCY. Review: effects of nitric oxide on eye diseases and their treatment. J Ocul Pharmacol Ther2001;17:189198
22 Beatty S, Koh H, Phil M, Henson D, Boulton M. Macular pigment and risk for agerelated macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci2001;42:439446 上一页 [1] [2] |
