人工光环境对视系统及性激素的影响及中药干预作用的研究
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摘要
本课题从动物实验和调查研究两方面诣在探讨人工光环境对视系统及生殖内分泌节律的影响,以及中药调周法对眼及生殖内分泌节律的保护与调整作用。
目的通过动物实验探讨人工光环境对大鼠眼部形态和功能以及生殖内分泌节律的影响,并观察复方中药制剂对眼及生殖内分泌节律的保护与调整作用。同时通过社会调查探讨不同光环境对人屈光状态、生育情况的影响。
方法实验研究部分:健康无任何眼病SD大鼠45只,随机分成3组,每组15只,对照组饲养在正常昼夜交替节律的环境中,接受自然界全光谱自然光线的照射,实验组分为模型组和中药组,饲养在光照控制箱内,接受人工光源循环照射,设定每目光照明(早6:00至晚24:00)、暗(晚24:00至早6:00)循环交替时间为18h/6h,同时中药组予以复方中药制剂灌胃。大鼠性成熟后,于动情周期前半期予以补阴方灌胃,动情周期后半期予以补阳方灌胃,实验第4月时,对各组大鼠行眼常规检查、视觉电生理检查、视网膜病理组织学检查、视网膜过氧化物以及抗氧化酶活性分析测定。阴道涂片确定大鼠处于动情间期,检测雌二醇含量。对使用实验光源进行光学参数测定。
社会调查部分:我们选取新疆维吾尔自治区伊犁哈萨克自治州哈萨克族人群进行社会调查研究。生活在牧区的哈萨克族人仍保持以自然光照为主的生活方式,人工光源照明时间很短;而城市哈萨克族人主要以人工光源照明为主,光照时间延长,这样同一种族的两组人群,处于不同的光环境,而原有的民族习惯基本不变,恰好符合了我们观察目标。我们于2005年11月至2006年11月随机调查成年哈萨克族人427例(828眼),年龄40-60岁,其中牧区哈萨克族人279例(546眼),城市哈萨克居民148例(282眼),性别不限,职业不限,因其它眼病而影响视力者不作为本次调查对象。对所有调查对象进行眼部检查,包括常规检查、裸眼视力检查、屈光状态检查,问卷调查,包括询问其户外活动时间、睡眠时间、照明时间以及照明光源类型、生育数量等。
结果实验研究部分:各组SD大鼠眼部大体组织结构未见明显差异。对照组视觉电生理检查波形较为典型,分化性好,模型组波形不典型,F-ERG与对照组比较Rod-R潜时延长,Max-R a,b波振幅显著下降,下降幅度分别为:54.26%,65.35%,b波潜时延长,Cone-R a,b波振幅下降,幅度分别为35.76%,38.46%,Ops OS值、30Hz Flicker N1-P1振幅下降,与对照组比较差异有显著性。F-VEP与对照组比较振幅降低,差异有显著性。中药组引出的波形与模型组较为相似,F-ERG与对照组比较Rod-R潜时延长,Max-R a,b波振幅显著下降,b波潜时延长,Cone-R a,b波振幅下降,Ops OS值、30Hz Flicker N1-P1振幅下降,与对照组比较差异有显著性。F-VEP与对照组比较振幅降低,差异有显著性。中药组与模型组比较Max-R b波波幅高,差异有显著性。对照组HE染色光镜观察见视网膜各层间分界清晰,内、外核层细胞核密集,胞核排列整齐规则,外核层约10～12个胞核厚度,内核层约4～5个胞核厚度,内丛状层疏松、网状,比外丛状层厚,神经节细胞核大,淡染,散在分部在神经纤维层内。模型组HE染色光镜下见视网膜普遍萎缩变薄,层次不清,层数减少,感光细胞内、外节结构消失,外核层和内核层分界不清,核层数减少,共约3～5个胞核厚度,核深染,排列紊乱,外丛状层消失,内丛状层变薄,神经节细胞水肿,稀疏,排列紊乱,神经纤维层水肿,变薄。中药组HE染色光镜下所见与模型组相类似。对照组大鼠视网膜MDA含量低,SOD活性高,与实验组有明显差异。中药组SOD活性比模型组高(P＜0.05)。对照组和用药组大鼠相对比较安静,实验组表现为比较惊觉,躁动不安,实验第4个月时于生殖间期检测各组血中雌激素含量,模型组大鼠血雌激素含量显著高于对照组、中药组。目光灯频闪大,稳定性差,紫外区的辐射非常明显。白炽灯发光亮度比较稳定,没有探测到紫外辐射区。
社会调查部分:城市哈萨克族人裸眼视力分布相对比较均匀,其中19%(54眼)视力为0.4-0.5,21%(59眼)视力为0.6-0.8,18%(50眼)视力为1.0以上者。而牧区哈萨克族人裸眼视力分布呈明显特点,主要集中在0.6以上,其中25%(137眼)视力为0.6-0.8,59%(319眼)视力在1.0以上。二组人群裸眼视力=1.0者,人群分布有显著性差异。城市哈萨克族人屈光度相对较多分布在平光和-4.0之间,而牧区哈萨克族人屈光度分布呈集中趋势,主要集中在≤+2.0D和≤-2.0D之间,其中45%(242眼)为平光,32%(168眼)为≤+2.0D,18%(101眼)为≤-2.0D。二组人群屈光度为=+2.0-平光和=-3.0以上者,人群分布有显著性差异。城市哈萨克族人主要在室内活动,日光灯为主要的照明光源,71%(105例)人工光源照射超过6小时。牧区哈萨克族人主要在室外活动,以自然界全光谱自然光照明为主,75%(210例)户外活动时间超过9小时以上,87%(242例)室内人工光源照明时间仅为1-3小时,白炽灯为主要照明光源。城市哈萨克居民生育数量少。
结论日光灯、白炽灯低强度人工光源长时间循环照射大鼠,对视网膜组织结构、视功能有一定影响,考虑与视网膜脂质过氧化有关,中药可能对视网膜内层具有一定的保护作用,但尚需通过大样本资料进一步深入研究加以证实。同时中药对调整大鼠生物节律紊乱有一定的作用,为临床上规范健康照明提供依据。光环境的变化可能是引起近视发病率增高的重要因素之一,有关发病机制还需进一步探讨,也许可为临床上预防近视提供新途径。人工光环境可能影响哈萨克族人生殖功能,尚需通过大样本资料进一步深入研究加以证实。作为近距离照明,传统的白炽灯对人眼损伤相对较小。
This topic studied the effects of low intensity artificial light on eye and on biothythm, the intervention role of traditional Chinese medicine to light damage to eye and biothythm disorder.
Objective:To study of artificial light on the eye and biothythm and traditional Chinese medicine intervention function by rats experiment.To study the effect of different light environment on refractive error and reproductive condition.
Methods:The first part:This experiment planed to simulate light environment of the human ordinary room.The SD rats were exposed to low intensity artificial light intermittently for a long time,daylight lamp and the incandescent lamp as experiment lamp.SD rats 45 without any eye diseases were divides into 3 groups randomly,each group of 15.The control group were exposed to natural light.Experimental group were divided into model group and traditional Chinese medicine group.Two experimental group were exposed to artificial light(light:dark=18:6h) which imitated indoor light of human.The rats of medicine group were given traditional Chinese medicine to fill the stomach according to rat reproductive period.After four months, routine inspection,F-ERG and F-VEP,retina histo-pathology inspection,estrogen content were carded throught to every group.Optical parameter was measured to daylight lamp and the incandescent lamp.The second part:We selected the Xinjiang Uigur Autonomous Region Yili kazak to conduct the social investigation research. Kazak who lived in the pastoral area still maintained traditional life style.Most of them used natural illumination.The artificial illumination time was very short.But the city Kazak illuminated mainly by the artificial light.The illumination time were longer than pastoral Kazak.Two groups of Kazak lived in the different light environment,but the original national custom was invariable.So two groups exactly conformed to us to observe the goal.From November,2005 to November,2006,We investigated grown-up Kazak 427 cases(828 eyes),the age 40-60 year old.The pastoral Kazak were 279 cases(546 eyes),the city Kazak 148 cases(282 eyes).There was no limit to occupation and sex.Anyone whose eye disease affected the vision were excluded.All objects were inspected,including the routine inspection,vision and refractive inspection,questionnaire survey.
Results:The first part:The eye tissue profile of each group had not seen the obvious difference.ERG and VEP of control group were more typical,but experiment group's were not.In model group,Latent period of Rod-R were prolonged.The amplitude of a-wave and b-wave of Max-R decreased by 54.26%and 65.35%respectively.The amplitude of a-wave and b-wave of Cone-R decreased by 35.76%and38.46% respectively.The amplitude of OS of Ops and N1-P1 of 30Hz Flicker decreased too. The amplitude of ERG in model group were lower than that in control group(P＜0.05).The amplitude of F-VEP in model group were lower than that in the control group(P＜0.05).ERG and VEP of medicine group were similar to model group,and b-wave of Max-R,Cone-R,Ops OS值、30Hz Flicker N1-P1 were lower than that of control group(P＜0.05).The amplitude of F-VEP were lower than that of control group(P＜0.05).The amplitude of b-wave of Max-R in medicine group were higher than model group.Retina was normal in the control group.The cell arrangement of the control group were clear and orderly by optical microscope.The outer nuclear layer were about 10 to 12 layer thickness,while the inner nuclear layer about 4 to 5.The inner plexiform layer were thicker than outer plexiform layer.The ganglion cell were in nerve fiber layer.The entire retina of the model group atrophied by optical microscope.The cell arrangement of the model group were disorderly.The outer and inner node of photoreceptors disappeared.There was no clear line between outer and inner nuclear layer.The nuclear layer reduced to about 3 to 5 layer thickness.The inner plexiform layer were thinner than that of control group.The ganglion cell and nerve fiber layer were swelled.What to see by optical microscope in medicine group were similar to model group.The control group MDA content were lower than that of two experiment group(P＜0.01).The control group SOD content were higher than that of two experiment group(P＜0.01).The medicine group SOD content were higher than that of model group(P＜0.01).SD rats of control or medicine group were quiet while model group were restless and alarmed.After 4 months,estrogen content in model group were higher than other two groups(P＜0.01).Daylight lamp brightness was not stable and contained much ultraviolet rays,but incandescent lamp was not.The second part:The city Kazak vision were worse.19%(54) the vision is 0.4-0.5,21%(59) the vision 0.6-0.8,18%(50) the vision above 1.0.But the pastoral Kazak vision were better.25%(137) the vision is 0.6-0.8,59%(319) the vision above 1.0.The number whose vision more than 1.0 in pastoral Ka7ak were more than city Kazak(P＜0.05).The city Kazak diopter were between 0D and—4.0D.But the pastoral Kazak diopter mainly concentrated between +2.0D and—2.0D,45%(242) 0D,32%(168)≤+2.0D,18%(101)≤—2.0D.Two groups diopters between +2.0D and 0D or less than 3.0 D have obvious difference.The city Kazak mainly were active in the room.The daylight lamp was the main illumination photosource. 71%(105 cases) the artificial light illuminated more than 6 hours.The pastoral Kazak were active mainly in the outdoor.75%(210 cases) the outdoors activity time were above 9 hours by the natural light illumination.87%(242 cases) the artificial light, main incandescent lamp,illumination time only were 1-3 hour.The number of reproduction were decreased.
Conclusion:It suggests that low intensity artificial light can injure retinal function and structure over a long period of time.At same time traditional Chinese medicine is helpful to regulate biothythm disorder.Maybe this medicine can protect retina too. But this opinion needs to discuss further.This research provides experimental basis for the improvement lighting installation.It infers that poor light environment is one of very important reasons to cause refractive error.At same time artifical light environment maybe effect reproductive ability.But this opinion needs to discuss further.
目的通过动物实验探讨人工光环境对大鼠眼部形态和功能以及生殖内分泌节律的影响,并观察复方中药制剂对眼及生殖内分泌节律的保护与调整作用。同时通过社会调查探讨不同光环境对人屈光状态、生育情况的影响。
方法实验研究部分:健康无任何眼病SD大鼠45只,随机分成3组,每组15只,对照组饲养在正常昼夜交替节律的环境中,接受自然界全光谱自然光线的照射,实验组分为模型组和中药组,饲养在光照控制箱内,接受人工光源循环照射,设定每目光照明(早6:00至晚24:00)、暗(晚24:00至早6:00)循环交替时间为18h/6h,同时中药组予以复方中药制剂灌胃。大鼠性成熟后,于动情周期前半期予以补阴方灌胃,动情周期后半期予以补阳方灌胃,实验第4月时,对各组大鼠行眼常规检查、视觉电生理检查、视网膜病理组织学检查、视网膜过氧化物以及抗氧化酶活性分析测定。阴道涂片确定大鼠处于动情间期,检测雌二醇含量。对使用实验光源进行光学参数测定。
社会调查部分:我们选取新疆维吾尔自治区伊犁哈萨克自治州哈萨克族人群进行社会调查研究。生活在牧区的哈萨克族人仍保持以自然光照为主的生活方式,人工光源照明时间很短;而城市哈萨克族人主要以人工光源照明为主,光照时间延长,这样同一种族的两组人群,处于不同的光环境,而原有的民族习惯基本不变,恰好符合了我们观察目标。我们于2005年11月至2006年11月随机调查成年哈萨克族人427例(828眼),年龄40-60岁,其中牧区哈萨克族人279例(546眼),城市哈萨克居民148例(282眼),性别不限,职业不限,因其它眼病而影响视力者不作为本次调查对象。对所有调查对象进行眼部检查,包括常规检查、裸眼视力检查、屈光状态检查,问卷调查,包括询问其户外活动时间、睡眠时间、照明时间以及照明光源类型、生育数量等。
结果实验研究部分:各组SD大鼠眼部大体组织结构未见明显差异。对照组视觉电生理检查波形较为典型,分化性好,模型组波形不典型,F-ERG与对照组比较Rod-R潜时延长,Max-R a,b波振幅显著下降,下降幅度分别为:54.26%,65.35%,b波潜时延长,Cone-R a,b波振幅下降,幅度分别为35.76%,38.46%,Ops OS值、30Hz Flicker N1-P1振幅下降,与对照组比较差异有显著性。F-VEP与对照组比较振幅降低,差异有显著性。中药组引出的波形与模型组较为相似,F-ERG与对照组比较Rod-R潜时延长,Max-R a,b波振幅显著下降,b波潜时延长,Cone-R a,b波振幅下降,Ops OS值、30Hz Flicker N1-P1振幅下降,与对照组比较差异有显著性。F-VEP与对照组比较振幅降低,差异有显著性。中药组与模型组比较Max-R b波波幅高,差异有显著性。对照组HE染色光镜观察见视网膜各层间分界清晰,内、外核层细胞核密集,胞核排列整齐规则,外核层约10～12个胞核厚度,内核层约4～5个胞核厚度,内丛状层疏松、网状,比外丛状层厚,神经节细胞核大,淡染,散在分部在神经纤维层内。模型组HE染色光镜下见视网膜普遍萎缩变薄,层次不清,层数减少,感光细胞内、外节结构消失,外核层和内核层分界不清,核层数减少,共约3～5个胞核厚度,核深染,排列紊乱,外丛状层消失,内丛状层变薄,神经节细胞水肿,稀疏,排列紊乱,神经纤维层水肿,变薄。中药组HE染色光镜下所见与模型组相类似。对照组大鼠视网膜MDA含量低,SOD活性高,与实验组有明显差异。中药组SOD活性比模型组高(P＜0.05)。对照组和用药组大鼠相对比较安静,实验组表现为比较惊觉,躁动不安,实验第4个月时于生殖间期检测各组血中雌激素含量,模型组大鼠血雌激素含量显著高于对照组、中药组。目光灯频闪大,稳定性差,紫外区的辐射非常明显。白炽灯发光亮度比较稳定,没有探测到紫外辐射区。
社会调查部分:城市哈萨克族人裸眼视力分布相对比较均匀,其中19%(54眼)视力为0.4-0.5,21%(59眼)视力为0.6-0.8,18%(50眼)视力为1.0以上者。而牧区哈萨克族人裸眼视力分布呈明显特点,主要集中在0.6以上,其中25%(137眼)视力为0.6-0.8,59%(319眼)视力在1.0以上。二组人群裸眼视力=1.0者,人群分布有显著性差异。城市哈萨克族人屈光度相对较多分布在平光和-4.0之间,而牧区哈萨克族人屈光度分布呈集中趋势,主要集中在≤+2.0D和≤-2.0D之间,其中45%(242眼)为平光,32%(168眼)为≤+2.0D,18%(101眼)为≤-2.0D。二组人群屈光度为=+2.0-平光和=-3.0以上者,人群分布有显著性差异。城市哈萨克族人主要在室内活动,日光灯为主要的照明光源,71%(105例)人工光源照射超过6小时。牧区哈萨克族人主要在室外活动,以自然界全光谱自然光照明为主,75%(210例)户外活动时间超过9小时以上,87%(242例)室内人工光源照明时间仅为1-3小时,白炽灯为主要照明光源。城市哈萨克居民生育数量少。
结论日光灯、白炽灯低强度人工光源长时间循环照射大鼠,对视网膜组织结构、视功能有一定影响,考虑与视网膜脂质过氧化有关,中药可能对视网膜内层具有一定的保护作用,但尚需通过大样本资料进一步深入研究加以证实。同时中药对调整大鼠生物节律紊乱有一定的作用,为临床上规范健康照明提供依据。光环境的变化可能是引起近视发病率增高的重要因素之一,有关发病机制还需进一步探讨,也许可为临床上预防近视提供新途径。人工光环境可能影响哈萨克族人生殖功能,尚需通过大样本资料进一步深入研究加以证实。作为近距离照明,传统的白炽灯对人眼损伤相对较小。
This topic studied the effects of low intensity artificial light on eye and on biothythm, the intervention role of traditional Chinese medicine to light damage to eye and biothythm disorder.
Objective:To study of artificial light on the eye and biothythm and traditional Chinese medicine intervention function by rats experiment.To study the effect of different light environment on refractive error and reproductive condition.
Methods:The first part:This experiment planed to simulate light environment of the human ordinary room.The SD rats were exposed to low intensity artificial light intermittently for a long time,daylight lamp and the incandescent lamp as experiment lamp.SD rats 45 without any eye diseases were divides into 3 groups randomly,each group of 15.The control group were exposed to natural light.Experimental group were divided into model group and traditional Chinese medicine group.Two experimental group were exposed to artificial light(light:dark=18:6h) which imitated indoor light of human.The rats of medicine group were given traditional Chinese medicine to fill the stomach according to rat reproductive period.After four months, routine inspection,F-ERG and F-VEP,retina histo-pathology inspection,estrogen content were carded throught to every group.Optical parameter was measured to daylight lamp and the incandescent lamp.The second part:We selected the Xinjiang Uigur Autonomous Region Yili kazak to conduct the social investigation research. Kazak who lived in the pastoral area still maintained traditional life style.Most of them used natural illumination.The artificial illumination time was very short.But the city Kazak illuminated mainly by the artificial light.The illumination time were longer than pastoral Kazak.Two groups of Kazak lived in the different light environment,but the original national custom was invariable.So two groups exactly conformed to us to observe the goal.From November,2005 to November,2006,We investigated grown-up Kazak 427 cases(828 eyes),the age 40-60 year old.The pastoral Kazak were 279 cases(546 eyes),the city Kazak 148 cases(282 eyes).There was no limit to occupation and sex.Anyone whose eye disease affected the vision were excluded.All objects were inspected,including the routine inspection,vision and refractive inspection,questionnaire survey.
Results:The first part:The eye tissue profile of each group had not seen the obvious difference.ERG and VEP of control group were more typical,but experiment group's were not.In model group,Latent period of Rod-R were prolonged.The amplitude of a-wave and b-wave of Max-R decreased by 54.26%and 65.35%respectively.The amplitude of a-wave and b-wave of Cone-R decreased by 35.76%and38.46% respectively.The amplitude of OS of Ops and N1-P1 of 30Hz Flicker decreased too. The amplitude of ERG in model group were lower than that in control group(P＜0.05).The amplitude of F-VEP in model group were lower than that in the control group(P＜0.05).ERG and VEP of medicine group were similar to model group,and b-wave of Max-R,Cone-R,Ops OS值、30Hz Flicker N1-P1 were lower than that of control group(P＜0.05).The amplitude of F-VEP were lower than that of control group(P＜0.05).The amplitude of b-wave of Max-R in medicine group were higher than model group.Retina was normal in the control group.The cell arrangement of the control group were clear and orderly by optical microscope.The outer nuclear layer were about 10 to 12 layer thickness,while the inner nuclear layer about 4 to 5.The inner plexiform layer were thicker than outer plexiform layer.The ganglion cell were in nerve fiber layer.The entire retina of the model group atrophied by optical microscope.The cell arrangement of the model group were disorderly.The outer and inner node of photoreceptors disappeared.There was no clear line between outer and inner nuclear layer.The nuclear layer reduced to about 3 to 5 layer thickness.The inner plexiform layer were thinner than that of control group.The ganglion cell and nerve fiber layer were swelled.What to see by optical microscope in medicine group were similar to model group.The control group MDA content were lower than that of two experiment group(P＜0.01).The control group SOD content were higher than that of two experiment group(P＜0.01).The medicine group SOD content were higher than that of model group(P＜0.01).SD rats of control or medicine group were quiet while model group were restless and alarmed.After 4 months,estrogen content in model group were higher than other two groups(P＜0.01).Daylight lamp brightness was not stable and contained much ultraviolet rays,but incandescent lamp was not.The second part:The city Kazak vision were worse.19%(54) the vision is 0.4-0.5,21%(59) the vision 0.6-0.8,18%(50) the vision above 1.0.But the pastoral Kazak vision were better.25%(137) the vision is 0.6-0.8,59%(319) the vision above 1.0.The number whose vision more than 1.0 in pastoral Ka7ak were more than city Kazak(P＜0.05).The city Kazak diopter were between 0D and—4.0D.But the pastoral Kazak diopter mainly concentrated between +2.0D and—2.0D,45%(242) 0D,32%(168)≤+2.0D,18%(101)≤—2.0D.Two groups diopters between +2.0D and 0D or less than 3.0 D have obvious difference.The city Kazak mainly were active in the room.The daylight lamp was the main illumination photosource. 71%(105 cases) the artificial light illuminated more than 6 hours.The pastoral Kazak were active mainly in the outdoor.75%(210 cases) the outdoors activity time were above 9 hours by the natural light illumination.87%(242 cases) the artificial light, main incandescent lamp,illumination time only were 1-3 hour.The number of reproduction were decreased.
Conclusion:It suggests that low intensity artificial light can injure retinal function and structure over a long period of time.At same time traditional Chinese medicine is helpful to regulate biothythm disorder.Maybe this medicine can protect retina too. But this opinion needs to discuss further.This research provides experimental basis for the improvement lighting installation.It infers that poor light environment is one of very important reasons to cause refractive error.At same time artifical light environment maybe effect reproductive ability.But this opinion needs to discuss further.
引文
1 Mainster MA,Ham WT Jr,Delori FC.Potential retinal hazards Instrument and environment light sources.Ophthalmol,1983,90(8):927-32
2 陈奇。《中药药理研究方法学》。北京:人民卫生出版社,2006,31
3 刘文舟,江文珊,段俊国等。几种常用实验动物的F-ERG和F-VEP检测。眼科新进展,2002,22(3):189-190
4 张作明,顾永昊,郭群等。小鼠与大鼠视网膜电图和闪光视觉诱发电位记录标准化方案建议。眼科新进展,2004,24(2):81-83
5 张式军。光污染—一种新型的环境污染。城市问题,2004,6:31-34
6 徐晓星。关于光污染概念问题的探讨。光源与照明,2005,3:23-24
7 李奇峰,肖辉,俞丽华。关于光污染。照明工程学报,2003,14(6):28-33
8 赵海天,向东。论广义灯光污染。中国照明电器,2003,6:6-10
9 年媛媛,刘稳华,范中和。城市环境与光污染。陕西师范大学学报(自然科学版),2005,33(6):64-65
10 张震,张效房。视网膜光损伤机制中NOS作用的实验研究。眼外伤职业眼病杂志,2005,27(4):246-248
11 李光玲,朱秀安。大鼠实验性视网膜光损伤中的视细胞凋亡。中华眼底病杂志,1999,15(3):167-169
12 Lee SJ,Montell C.Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway.Curr Biol,2004,14(23):2076-85
13 Logvinov SV,Potapov AV,Varakuta EY.Dynamics of structural changes in the retina during long-term exposure to bright light.Bull Exp Biol Med,2003,136(4):411-4
14 张纯 王薇。大鼠光损伤性内层视网膜变性的超微病理学研究。中华眼底病杂志,2003,19(4):222-225
15 Meyers SM,Ostrovsky MA,Bonner RF.A model of spectral filtering to reduce photochemical damage in age-related macular degeneration.Trans Am Ophthalmol Soc,2004,102:83-96
16 Hochheimer BF,Danna SA,Calkins JL.Retinal damage from light.Am J Ophthalmol,1979,88(6):1039-44
17 Berler DK,Peyser R.Light intensity and visual acuity following cataract surgery.Ophthalmol,1983,90(8):933-36
18 McDonald HR,Irvine AR.Light-induced maculopathy from the operating microscope in extracapsular cataract extraction and intraocular lens implantation.Ophthalmol,1983,90(8):945-51
19 Richards A,Emondi AA,Rohrer B. Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes.Vis Neurosci,2006,23(1):91-7
20 Takahashi T,Machida S,Masuda T,et al.Functional changes in rod and cone pathways after photoreceptor loss in light-damaged rats.Curr Eye Res,2005,30(8):703-13
21 Kong L, Li F, Soleman CE, et al. Bright cyclic light accelerates photoreceptor cell degeneration in tubby mice.Neurobiol Dis, 2006, 21(3):468-77
22 Vaughan DK, Peachey NS, Richards MJ. Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Exp Eye Res, 2006,82(3):496-504
23 Kim SR,Nakanishi K,Itagaki Y,Sparrow JR. Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin.Exp Eye Res, 2006,82(5):828-39
24 Krinsky NI,Landrum JT,Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.Annu Rev Nutr, 2003,23:171-201
25 Desmettre T,Lecerf JM,Souied EH. Nutrition and age-related macular degeneration.J Fr Ophtalmol,2004,27(9 ):3S38-56
26 Rapp LM, Smith SC.Morphologic comparisons between rhodopsin-mediated and short-wavelength classes of retinal light damage.Invest Ophthalmol Vis Sci, 1992,33:3367-3377
27 Grimm C,Wenzel A,Williams T,et al. Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.Invest Ophthalmol Vis Sci, 2001,42(2):497-505
28 Keller C,Grimm C,Wenzel A,et al. Protective effect of halothane anesthesia on retinal light damage: inhibition of metabolic rhodopsin regeneration.Invest Opthalmol Vis Sci, 2001 Feb,42(2):476-80
29 Yang JH, Basinger SF, Gross RL,et al. Blue Light-Induced Generation of Reactive Oxygen Species in Photoreceptor Ellipsoids Requires Mitochondrial Electron Transport. Investigative Ophthalmology and Visual Science,2003,44:1312-1319
30 Augustin AJ,Dick HB,Offermann Let al. The significance of oxidative mechanisms in diseases of the retina.Klin Monatsbl Augenheilkd, 2002,219(9):631-43
31 Godley BF,Shamsi FA, Liang FQ,et al. Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells. J Biol Chem,2005,280(22): 21061-21066
32 Jang YP,Matsuda H,Itagaki Y,et al. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin.J Biol Chem,2005,280(48):39732-9
33 Wihlmark U,Wrigstad A,Roberg K,et al. Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation.Free Radic Biol Med,1997,22(7):1229-34
34 Vihtelic TS,Hyde DR.Light-induced rod and cone cell death and regeneration in the adult albino zebrafish(Danio rerio) retina.J Neurobiol,2000,44(3):289-307
35 Hafezi F,Marti A,Grimm C,et al.Differential DNA binding activities of the transcription factors AP-1 and Oct-1 during light-induced apoptosis of photoreceptors.Vision Res,1999,39:2511-2518
36 金祥娜,万青.视网膜光化学损伤后MDA、SOD及NO浓度变化的研究。眼科研究,2005,23(6):301-303
37 Wassell J,Davies S,Bardsley W,et al.The photo reactivity of the retinal age pigment lipofuscin.J Biol Chem,1999,274:23828-23832
38 李文松,方谦逊,罗成仁,等。光氧化损伤中过氧化物歧化酶和过氧化脂质变化。眼底病,1993,9:14
39 Hammond CJ,Sneider H,Gilbert CE,et al.Gene and environment in refractive error:the twin eye study.Invest Ophthalmol Vis Sci,2001,42:1232-1236
40 Mutti DO,Mitchell GL,Moeschberger ML,et al.Parental myopia,near work,school achievement,and children's refractive error.Invest Ophthalmol Vis,2002,43:332-330
41 Liang CL,Wang HS,Hung KS,et al.Evaluation of MMP3 and TIMP1 as candidate genes for high myopia in young Taiwanese men.Am J Ophthalmol,2006,142(3):518-20
42 Hung GK,Ciuffreda KJ.Model of human refractive error development.Curr Eye Res,1999,19(1):41-52.
43 王一心,孙建军,李梦秋。阿克苏市维吾尔族和汉族中学生视力调查。中国中医眼科杂志,2007,17(1):42-45
44 Ciuffreda KJ,Waallis DM.Myopes show increased susceptibility to nearwork after effects.Invest Ophthalmol Vis Sci,1998,39(10):1797-1803
45 TY Wong,PJ Foster,GJ Johnson,et al.Education,socioeconomic status,and ocular dimensions in Chinese adults:the Tanjong Pagar Survey.Br J Ophthalmolog,2002,86(9):963-968
46 Shimizu N,Nomura H,Ando F,et al.Refractive errors and factors associated with myopia in an adult Japanese population.Jpn J Ophthalmol,2003,47(1):6-12
47 Loman Jane,Quin Graham E,Kamoun Lay la,et al.Darkness and nearwork:myopia and its progression in third-year law students.Ophrhalmology,2002:109(5):1032-1038
48 张彩霞,郝小波,唐忠鲁。近视眼发生的环境因素与中医药防治。广西中医学院学报,2005,8(1):71-72
49 Wensor M,McCarty CA,Taylor HR.Prevalence and risk factors of myopia in Victoria,Australia.Arch Ophthalmol,1999,117(5):658-663
50 Katz J,Tielsh JM,Sommer A,et al.Prevalence and risk factors for refractive errors in an adult inner city population.Invest Ophthalmol Vis Sci,1997,389(2):334
51 Foster RG,Aragmaso S,Coleman S,et al.Photoreceptors regulating circadian behavior:a mouse model.J Biol Rhythms,1993,8 Suppl:S17-23
52 Thompson C,Rickman CB,Shaw S,et al.Expression of the Blue-Light Receptor Cryptochrome in the Human Retina.Investigative Ophthalmology and Visual Science,2003,44:4515-4521
53 Van der Horst GT,Muijtjens M,Kobayashi K,et al.Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.Nature,1999,398:627-30
54 Eun BK,Lee B,Kang H.Cloning and Expression of Cryptochrome2 cDNA in the Rat.Molecules and cells,2001,12(3):286-291
55 Foster RG,Aragmaso S,Coleman S,et al.Photoreceptors regulating circadian behavior:a mouse model.J Biol Rhythms,1993,8 Suppl:S17-23
56 Pauley SM.Lighting for the human circadian clock:recent research indicates that lighting has become a public health issue.Med Hypotheses,2004,63(4):588-96
57 Hansen J.Increased breast cancer risk among women who work predominantly at night.Epidemiology,2001,12(1):74-77
58 Schernhammer ES,Laden F,et al.Rotating night shifts and risk of breast cancer in women participating in the nurses health study.J Natl Cancer Inst,2001,93(20):1563-1568
59 王国卿,童建。松果体昼夜节律生物钟分子机制的研究进展。生理科学进展,2004,35(3):210-214
60 谈勇等。补肾调周法在体外受精-胚移植期前应用的临床观察。中国中医药信息杂志,2001,(12)
61 江舟,刘延友,郭莉,等。不同周期光暗循环对小鼠生长的影响。西部医学,2005,17(2):97-101
62 杨波,刘延友,汪宇辉,等。不同光暗循环下小鼠自发活动生物节律周期的频率分析。航天医学与医学工程,2006,19(3):179-182
63 连祥霖,郭冰云,游彩惠。光照制对大鼠ALAD活性与Hb含量昼夜节律的影响。卫生毒理学杂志,1999,13(2):130-131
64 杨华,连祥霖,徐美华。光照制对大鼠脂质3指标昼夜节律的影响。海峡预防医学杂志,2005,11(1):8-10
65 Grimm C,Wenzel A,Williams T,et al.Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.Invest Ophthalmol Vis Sci, 2001,42(2):497-505
66 Wu J,Gorman A,Zhou X,et al. Involvement of caspase-3 in photoreceptor cell apoptosis induced by in vivo blue light exposure.Invest Ophthalmol Vis Sci, 2002,43(10):3349-54
67 Rozanowska M,Jarvis-Evans J,Korytowski W,et al. Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species.J Biol Chem, 1995, 11,270(32):18825-30
68 King A,Gottlied E,Brooks DG,et al. Mitochondria-derived reactive oxygen species mediate blue light-induced death of retinal pigment epithelial cells.Photochem Photobiol, 2004,79(5):470-5
69 Wu J,Seregard S,Spangberg B,et al. Blue light induced apoptosis in rat retina.Eye, 1999,13 :577-83
70 Jang YP,Matsuda H,Itagaki Y,et al. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin.J Biol Chem,2005,280(48):39732-9
71 Chen E,Pallon J,Forslind B. Distribution of calcium and sulphur in the blue-light-exposed rat retina.Graefes Arch Clin Exp Ophthalmol, 1995,233(3):163-7
72 Chen E. Inhibition of enzymes by short-wave optical radiation and its effect on the retina.Acta Ophthalmol Suppl, 1993;(208):1-50
73 Hanna N,Peri KG,Abran D,et al. light induces peroxidation in retina by activating prostaglandin G/H synthase.Free Radic Biol Med, 1997,23(6):885-97
74 Schwartz L,Boelle PY,Dhermies F,et al. Blue light dose distribution and retinitis pigmentosa visual field defects: an hypothesis.Med Hypotheses, 2003 ,60(5):644-9
75 Li C,Tang Y,Li F,et al. 17beta-estradiol (betaE2) protects human retinal Muller cell against oxidative stress in vitro: evaluation of its effects on gene expression by cDNA microarray.Glia, 2006,53(4):392-400
76 Algvere PV,Marshall J,Seregard S. Age-related maculopathy and the impact of blue light hazard.Acta Ophthalmol Scand, 2006 ,84(1):4-15
77 Smith BT,Belani S,Ho AC. Light energy, cataract surgery, and progression of age-related macular degeneration.Curr Ophthalmol, 2005,16(3):166-9
78 Krinsky NI,Landrum JT,Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.Annu Rev Nutr, 2003,23:171-201
2 陈奇。《中药药理研究方法学》。北京:人民卫生出版社,2006,31
3 刘文舟,江文珊,段俊国等。几种常用实验动物的F-ERG和F-VEP检测。眼科新进展,2002,22(3):189-190
4 张作明,顾永昊,郭群等。小鼠与大鼠视网膜电图和闪光视觉诱发电位记录标准化方案建议。眼科新进展,2004,24(2):81-83
5 张式军。光污染—一种新型的环境污染。城市问题,2004,6:31-34
6 徐晓星。关于光污染概念问题的探讨。光源与照明,2005,3:23-24
7 李奇峰,肖辉,俞丽华。关于光污染。照明工程学报,2003,14(6):28-33
8 赵海天,向东。论广义灯光污染。中国照明电器,2003,6:6-10
9 年媛媛,刘稳华,范中和。城市环境与光污染。陕西师范大学学报(自然科学版),2005,33(6):64-65
10 张震,张效房。视网膜光损伤机制中NOS作用的实验研究。眼外伤职业眼病杂志,2005,27(4):246-248
11 李光玲,朱秀安。大鼠实验性视网膜光损伤中的视细胞凋亡。中华眼底病杂志,1999,15(3):167-169
12 Lee SJ,Montell C.Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway.Curr Biol,2004,14(23):2076-85
13 Logvinov SV,Potapov AV,Varakuta EY.Dynamics of structural changes in the retina during long-term exposure to bright light.Bull Exp Biol Med,2003,136(4):411-4
14 张纯 王薇。大鼠光损伤性内层视网膜变性的超微病理学研究。中华眼底病杂志,2003,19(4):222-225
15 Meyers SM,Ostrovsky MA,Bonner RF.A model of spectral filtering to reduce photochemical damage in age-related macular degeneration.Trans Am Ophthalmol Soc,2004,102:83-96
16 Hochheimer BF,Danna SA,Calkins JL.Retinal damage from light.Am J Ophthalmol,1979,88(6):1039-44
17 Berler DK,Peyser R.Light intensity and visual acuity following cataract surgery.Ophthalmol,1983,90(8):933-36
18 McDonald HR,Irvine AR.Light-induced maculopathy from the operating microscope in extracapsular cataract extraction and intraocular lens implantation.Ophthalmol,1983,90(8):945-51
19 Richards A,Emondi AA,Rohrer B. Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes.Vis Neurosci,2006,23(1):91-7
20 Takahashi T,Machida S,Masuda T,et al.Functional changes in rod and cone pathways after photoreceptor loss in light-damaged rats.Curr Eye Res,2005,30(8):703-13
21 Kong L, Li F, Soleman CE, et al. Bright cyclic light accelerates photoreceptor cell degeneration in tubby mice.Neurobiol Dis, 2006, 21(3):468-77
22 Vaughan DK, Peachey NS, Richards MJ. Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Exp Eye Res, 2006,82(3):496-504
23 Kim SR,Nakanishi K,Itagaki Y,Sparrow JR. Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin.Exp Eye Res, 2006,82(5):828-39
24 Krinsky NI,Landrum JT,Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.Annu Rev Nutr, 2003,23:171-201
25 Desmettre T,Lecerf JM,Souied EH. Nutrition and age-related macular degeneration.J Fr Ophtalmol,2004,27(9 ):3S38-56
26 Rapp LM, Smith SC.Morphologic comparisons between rhodopsin-mediated and short-wavelength classes of retinal light damage.Invest Ophthalmol Vis Sci, 1992,33:3367-3377
27 Grimm C,Wenzel A,Williams T,et al. Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.Invest Ophthalmol Vis Sci, 2001,42(2):497-505
28 Keller C,Grimm C,Wenzel A,et al. Protective effect of halothane anesthesia on retinal light damage: inhibition of metabolic rhodopsin regeneration.Invest Opthalmol Vis Sci, 2001 Feb,42(2):476-80
29 Yang JH, Basinger SF, Gross RL,et al. Blue Light-Induced Generation of Reactive Oxygen Species in Photoreceptor Ellipsoids Requires Mitochondrial Electron Transport. Investigative Ophthalmology and Visual Science,2003,44:1312-1319
30 Augustin AJ,Dick HB,Offermann Let al. The significance of oxidative mechanisms in diseases of the retina.Klin Monatsbl Augenheilkd, 2002,219(9):631-43
31 Godley BF,Shamsi FA, Liang FQ,et al. Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells. J Biol Chem,2005,280(22): 21061-21066
32 Jang YP,Matsuda H,Itagaki Y,et al. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin.J Biol Chem,2005,280(48):39732-9
33 Wihlmark U,Wrigstad A,Roberg K,et al. Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation.Free Radic Biol Med,1997,22(7):1229-34
34 Vihtelic TS,Hyde DR.Light-induced rod and cone cell death and regeneration in the adult albino zebrafish(Danio rerio) retina.J Neurobiol,2000,44(3):289-307
35 Hafezi F,Marti A,Grimm C,et al.Differential DNA binding activities of the transcription factors AP-1 and Oct-1 during light-induced apoptosis of photoreceptors.Vision Res,1999,39:2511-2518
36 金祥娜,万青.视网膜光化学损伤后MDA、SOD及NO浓度变化的研究。眼科研究,2005,23(6):301-303
37 Wassell J,Davies S,Bardsley W,et al.The photo reactivity of the retinal age pigment lipofuscin.J Biol Chem,1999,274:23828-23832
38 李文松,方谦逊,罗成仁,等。光氧化损伤中过氧化物歧化酶和过氧化脂质变化。眼底病,1993,9:14
39 Hammond CJ,Sneider H,Gilbert CE,et al.Gene and environment in refractive error:the twin eye study.Invest Ophthalmol Vis Sci,2001,42:1232-1236
40 Mutti DO,Mitchell GL,Moeschberger ML,et al.Parental myopia,near work,school achievement,and children's refractive error.Invest Ophthalmol Vis,2002,43:332-330
41 Liang CL,Wang HS,Hung KS,et al.Evaluation of MMP3 and TIMP1 as candidate genes for high myopia in young Taiwanese men.Am J Ophthalmol,2006,142(3):518-20
42 Hung GK,Ciuffreda KJ.Model of human refractive error development.Curr Eye Res,1999,19(1):41-52.
43 王一心,孙建军,李梦秋。阿克苏市维吾尔族和汉族中学生视力调查。中国中医眼科杂志,2007,17(1):42-45
44 Ciuffreda KJ,Waallis DM.Myopes show increased susceptibility to nearwork after effects.Invest Ophthalmol Vis Sci,1998,39(10):1797-1803
45 TY Wong,PJ Foster,GJ Johnson,et al.Education,socioeconomic status,and ocular dimensions in Chinese adults:the Tanjong Pagar Survey.Br J Ophthalmolog,2002,86(9):963-968
46 Shimizu N,Nomura H,Ando F,et al.Refractive errors and factors associated with myopia in an adult Japanese population.Jpn J Ophthalmol,2003,47(1):6-12
47 Loman Jane,Quin Graham E,Kamoun Lay la,et al.Darkness and nearwork:myopia and its progression in third-year law students.Ophrhalmology,2002:109(5):1032-1038
48 张彩霞,郝小波,唐忠鲁。近视眼发生的环境因素与中医药防治。广西中医学院学报,2005,8(1):71-72
49 Wensor M,McCarty CA,Taylor HR.Prevalence and risk factors of myopia in Victoria,Australia.Arch Ophthalmol,1999,117(5):658-663
50 Katz J,Tielsh JM,Sommer A,et al.Prevalence and risk factors for refractive errors in an adult inner city population.Invest Ophthalmol Vis Sci,1997,389(2):334
51 Foster RG,Aragmaso S,Coleman S,et al.Photoreceptors regulating circadian behavior:a mouse model.J Biol Rhythms,1993,8 Suppl:S17-23
52 Thompson C,Rickman CB,Shaw S,et al.Expression of the Blue-Light Receptor Cryptochrome in the Human Retina.Investigative Ophthalmology and Visual Science,2003,44:4515-4521
53 Van der Horst GT,Muijtjens M,Kobayashi K,et al.Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.Nature,1999,398:627-30
54 Eun BK,Lee B,Kang H.Cloning and Expression of Cryptochrome2 cDNA in the Rat.Molecules and cells,2001,12(3):286-291
55 Foster RG,Aragmaso S,Coleman S,et al.Photoreceptors regulating circadian behavior:a mouse model.J Biol Rhythms,1993,8 Suppl:S17-23
56 Pauley SM.Lighting for the human circadian clock:recent research indicates that lighting has become a public health issue.Med Hypotheses,2004,63(4):588-96
57 Hansen J.Increased breast cancer risk among women who work predominantly at night.Epidemiology,2001,12(1):74-77
58 Schernhammer ES,Laden F,et al.Rotating night shifts and risk of breast cancer in women participating in the nurses health study.J Natl Cancer Inst,2001,93(20):1563-1568
59 王国卿,童建。松果体昼夜节律生物钟分子机制的研究进展。生理科学进展,2004,35(3):210-214
60 谈勇等。补肾调周法在体外受精-胚移植期前应用的临床观察。中国中医药信息杂志,2001,(12)
61 江舟,刘延友,郭莉,等。不同周期光暗循环对小鼠生长的影响。西部医学,2005,17(2):97-101
62 杨波,刘延友,汪宇辉,等。不同光暗循环下小鼠自发活动生物节律周期的频率分析。航天医学与医学工程,2006,19(3):179-182
63 连祥霖,郭冰云,游彩惠。光照制对大鼠ALAD活性与Hb含量昼夜节律的影响。卫生毒理学杂志,1999,13(2):130-131
64 杨华,连祥霖,徐美华。光照制对大鼠脂质3指标昼夜节律的影响。海峡预防医学杂志,2005,11(1):8-10
65 Grimm C,Wenzel A,Williams T,et al.Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.Invest Ophthalmol Vis Sci, 2001,42(2):497-505
66 Wu J,Gorman A,Zhou X,et al. Involvement of caspase-3 in photoreceptor cell apoptosis induced by in vivo blue light exposure.Invest Ophthalmol Vis Sci, 2002,43(10):3349-54
67 Rozanowska M,Jarvis-Evans J,Korytowski W,et al. Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species.J Biol Chem, 1995, 11,270(32):18825-30
68 King A,Gottlied E,Brooks DG,et al. Mitochondria-derived reactive oxygen species mediate blue light-induced death of retinal pigment epithelial cells.Photochem Photobiol, 2004,79(5):470-5
69 Wu J,Seregard S,Spangberg B,et al. Blue light induced apoptosis in rat retina.Eye, 1999,13 :577-83
70 Jang YP,Matsuda H,Itagaki Y,et al. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin.J Biol Chem,2005,280(48):39732-9
71 Chen E,Pallon J,Forslind B. Distribution of calcium and sulphur in the blue-light-exposed rat retina.Graefes Arch Clin Exp Ophthalmol, 1995,233(3):163-7
72 Chen E. Inhibition of enzymes by short-wave optical radiation and its effect on the retina.Acta Ophthalmol Suppl, 1993;(208):1-50
73 Hanna N,Peri KG,Abran D,et al. light induces peroxidation in retina by activating prostaglandin G/H synthase.Free Radic Biol Med, 1997,23(6):885-97
74 Schwartz L,Boelle PY,Dhermies F,et al. Blue light dose distribution and retinitis pigmentosa visual field defects: an hypothesis.Med Hypotheses, 2003 ,60(5):644-9
75 Li C,Tang Y,Li F,et al. 17beta-estradiol (betaE2) protects human retinal Muller cell against oxidative stress in vitro: evaluation of its effects on gene expression by cDNA microarray.Glia, 2006,53(4):392-400
76 Algvere PV,Marshall J,Seregard S. Age-related maculopathy and the impact of blue light hazard.Acta Ophthalmol Scand, 2006 ,84(1):4-15
77 Smith BT,Belani S,Ho AC. Light energy, cataract surgery, and progression of age-related macular degeneration.Curr Ophthalmol, 2005,16(3):166-9
78 Krinsky NI,Landrum JT,Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.Annu Rev Nutr, 2003,23:171-201