实验研究
ENGLISH ABSTRACT
蓝光对豚鼠离焦性近视进展的抑制作用及其视锥细胞密度变化机制
邹蕾蕾
刘睿
刘红
戴锦晖
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20221018-00484
Inhibitory effect of blue light intervention on lens-induced myopia development in guinea pigs and the mechanism of cone density change
Zou Leilei
Liu Rui
Liu Hong
Dai Jinhui
Authors Info & Affiliations
Zou Leilei
Department of Ophthalmology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350011, China
Liu Rui
Eye and ENT Hospital of Fudan University, Shanghai 200031, China
Liu Hong
Department of Ophthalmology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350011, China
Dai Jinhui
Department of Ophthalmology, Zhongshan Hospital of Fudan University, Shanghai 310000, China
·
DOI: 10.3760/cma.j.cn115989-20221018-00484
0
0
0
0
0
0
PDF下载
APP内阅读
摘要

目的观察蓝光干预对光学离焦性近视豚鼠屈光发育的影响及其作用机制。

方法选取普通级2周龄三色豚鼠48只,采用抛硬币法随机分成蓝光组和白光组,每组各24只。所有豚鼠右眼佩戴-5.00 D镜片建立光学离焦模型,为实验眼;左眼为自身对照,不予遮盖。实验前及实验开始后8周,采用带状光检影镜测量豚鼠屈光度,A型超声测量前房深度、晶状体厚度及眼轴长度,角膜曲率计测量角膜曲率半径。实验开始后8周,采用过量麻醉法处死豚鼠,取右眼眼球并分离视网膜,采用视网膜铺片免疫荧光染色观察豚鼠视网膜S及M视锥细胞密度;采用高效液相色谱分析法检测视网膜视黄酸表达;采用实时荧光定量PCR检测视网膜视黄酸受体(RAR-β)和巩膜中基质金属蛋白酶2(MMP-2)、组织金属蛋白酶抑制剂2(TIMP-2)及Ⅰ型胶原的表达;采用苏木精-伊红染色观察巩膜厚度变化。

结果实验开始后8周,蓝光组实验眼较白光组实验眼出现(0.63±0.12)D相对远视,眼轴增长延缓(0.08±0.00)mm;蓝光组对照眼较白光组对照眼出现(0.42±0.09)D相对远视,眼轴增长延缓(0.08±0.00)mm;蓝光组实验眼较蓝光组对照眼近视加深(1.52±0.09)D,眼轴增长(0.06±0.00)mm;白光组实验眼较白光组对照眼近视加深(1.66±0.07)D,眼轴增长(0.13±0.00)mm,差异均有统计学意义(均P<0.05)。蓝光组豚鼠视网膜背侧和腹侧M视锥细胞密度小于白光组,背侧和腹侧S视锥细胞密度大于白光组,差异均有统计学意义(t=32.33、52.23、42.09、25.02,均P<0.05)。蓝光干预后近视延缓与腹侧S视锥细胞密度增加呈强正相关(r=0.95,P<0.01)。蓝光组视黄酸含量、RAR-β和MMP-2相对表达量较白光组减少,TIMP-2和Ⅰ型胶原相对表达量较白光组增加,差异均有统计学意义(t=18.73、7.45、3.72、6.19、9.03,均P<0.05)。蓝光组巩膜厚度为(125.0±7.8)μm,较白光组的(102.0±6.3)μm明显增厚,差异有统计学意义(t=26.93,P<0.05)。

结论蓝光可抑制豚鼠离焦性近视进展;豚鼠屈光度的改变可能通过视网膜视锥细胞密度变化影响视网膜视黄酸及巩膜胶原的表达来实现。

近视;豚鼠;视锥细胞;视黄酸;蓝光;离焦性近视
ABSTRACT

ObjectiveTo observe the effects of blue light intervention on the development of optical defocus-induced myopia in guinea pigs and investigate its underlying mechanisms.

MethodsForty-eight normal-grade two-week-old tricolor guinea pigs were randomly divided into a blue light group and a white light group, with 24 animals in each group.The right eye of guinea pigs was fitted with a -5.00 D lens to establish an optical defocus model as the experimental eye, while the left eye served as the control without any covering.Before the experiment and after 8-week intervention, the refractive power of guinea pigs was measured by streak retinoscopy.The anterior chamber depth, lens thickness, and axial length were measured by A-scan ultrasonography.Corneal curvature radius was determined using a keratometer.After 8-week intervention, the guinea pigs were euthanized through overanesthesia, and the right eyeballs were enucleated and the retinas were isolated.The density of S and M cone cells of the guinea pig retinal sections were observed via immunofluorescence staining.The expression of retinal retinoic acid was assessed by high-performance liquid chromatography.The expressions of retinoic acid receptor (RAR-β) in the retina and matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type Ⅰ collagen in the sclera were detected by real-time fluorescence quantitative PCR.Changes in scleral thickness were observed through hematoxylin-eosin staining.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Eye and ENT Hospital of Fudan University (No.2022ETKLD10032).

ResultsAfter 8 weeks of intervention, guinea pigs in the blue light group showed (0.63±0.12)D of relative hyperopia and a deceleration of axial elongation by (0.08±0.00)mm compared with the white light group in the right eye.In the left eye, guinea pigs in the blue light group showed (0.42±0.09)D of relative hyperopia and a deceleration of axial elongation by (0.08±0.00)mm compared with the white light group.The guinea pigs in blue light group showed (1.52±0.09)D of myopia in the right eye compared with the left eye, with an increase in axial elongation of (0.06±0.00)mm.The guinea pigs in white light group showed (1.66±0.07)D of myopia in the right eye compared with the left eye, with an increase in axial elongation of (0.13±0.00)mm, and the differences were statistically significant (all at P<0.05). The density of M cone cells was lower and density of S cone cells was higher in the blue light group in the dorsal and ventral sides of the retinal sections compared with the white light group, showing statistically significant differences (t=32.33, 52.23, 42.09, 25.02; all at P<0.05). The deceleration of myopia progression in the blue light group was strongly positively correlated with the increase in S cone cell density on the ventral side (r=0.95, P<0.01). The expression levels of retinoic acid, RAR-β, and MMP-2 were decreased, and expression levels of TIMP-2 and type Ⅰ collagen were increased in blue light group compared with the white light group, showing statistically significant differences (t=18.73, 7.45, 3.72, 6.19, 9.03; all at P<0.05). The scleral thickness in the blue light group was (125.0±7.8)μm, which was significantly thicker than (102.0±6.3)μm in the white light group (t=26.93, P<0.05).

ConclusionsBlue light intervention can inhibit the progression of defocus-induced myopia in guinea pigs.Refractive power changes in guinea pigs may be influenced by alterations in retinal cone cell density, retinoic acid expression, and scleral collagen expression.

Myopia;Guinea pigs;Retinal cone photoreceptor cells;Retinoic acid;Blue light;Defocus-induced myopia
Dai Jinhui, Email: mocdef.6ab218iuhnijiad
Liu Hong, Email: tendef.3ab62fezgnohuil

Zou Leilei and Liu Rui contributed equally to the article

引用本文

邹蕾蕾,刘睿,刘红,等. 蓝光对豚鼠离焦性近视进展的抑制作用及其视锥细胞密度变化机制[J]. 中华实验眼科杂志,2023,41(08):730-738.

DOI:10.3760/cma.j.cn115989-20221018-00484

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价
近视已成为世界性的公共卫生问题,虽然在流行病学研究中发现临床应用角膜塑形镜、离焦框架眼镜及低浓度阿托品可以延缓近视进展,但其有效性均存在个体差异。目前针对近视发病机制的基础研究主要集中在形觉剥夺和光学离焦2种动物模型[ 1 , 2 , 3 ]。色光作为视觉信息的重要组成部分,在眼正视化过程中同样发挥着重要作用[ 4 ]。在豚鼠、鸡、小鼠等动物模型研究中发现,短波长光抑制正视化进展,中/长波长光促进正视化进展[ 5 , 6 , 7 ]。但在恒河猴及树鼩动物模型中发现了相反的结果,长波长光可抑制正视化进展[ 8 , 9 ]。色光可影响屈光发育,但其具体机制尚不清楚。豚鼠是一种二色视动物,视网膜上有S及M视锥细胞,分布具有特征性,即背侧以表达M视蛋白的M视锥细胞为主,腹侧以表达S视蛋白的S视锥细胞为主,中间过渡区主要为共表达S及M视蛋白的视锥细胞。本课题组前期研究发现豚鼠在蓝光干预后,屈光状态偏远视,同时S视锥细胞密度增加;在绿光干预后,屈光状态偏近视,M视锥细胞密度增加[ 10 ]。此外,研究发现蓝光及绿光干预下豚鼠眼球背侧及腹侧屈光发育不同,绿光中眼球背侧正视化加速更明显;蓝光中眼球腹侧正视化延缓更明显[ 11 ]。这种区域性的屈光度改变差异可能与视锥细胞的特征性分布有关。蓝光干预的豚鼠离焦性近视模型中屈光度与视锥细胞密度的关系尚不清楚。此外,巩膜胶原的重塑是近视加深、眼轴延长的一个主要因素。在近视动物实验中发现,巩膜中的基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)及组织金属蛋白酶抑制剂2(tissue inhibitor of metalloproteinases-2,TIMP-2)是调控巩膜胶原合成与降解的关键因子[ 12 ]。本研究通过建立蓝光干预的豚鼠离焦性近视模型,研究近视与豚鼠视网膜S及M视锥细胞密度的关系,并检测视锥细胞的代谢产物视黄酸、视黄酸受体(retinoic acid receptor,RAR-β)以及近视发生的最终效应器——巩膜中MMP-2/TIMP-2及胶原等的改变,从而探讨蓝光干预近视进展的可能机制。
试读结束,您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Wiesel TN , Raviola E Myopia and eye enlargement after neonatal lid fusion in monkeys[J]Nature 1977,266(5597):66-68. DOI: 10.1038/266066a0 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Huo L , Cui D , Yang X et al. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta[J]Mol Vis 2013,19:1795-1803.
返回引文位置Google Scholar
百度学术
万方数据
[3]
李聪颖甘嘉禾王美君不同强度光照对豚鼠屈光发育和形觉剥夺性近视的影响[J]中华实验眼科杂志 2022,40(6):491-497. DOI: 10.3760/cma.j.cn115989-20220228-00079 .
返回引文位置Google Scholar
百度学术
万方数据
Li CY , Gan JH , Wang MJ et al. Effects of different intensity of lighting on refractive development and form deprivation myopia in guinea pigs[J]Chin J Exp Ophthalmol 2022,40(6):491-497. DOI: 10.3760/cma.j.cn115989-20220228-00079 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[4]
刘鹏飞肖林畅立斌短波长单色光干预形觉剥夺性近视发展的实验研究[J]中华实验眼科杂志 2013,31(10):925-929. DOI: 10.3760/cma.j.issn.2095-0160.2013.10.005 .
返回引文位置Google Scholar
百度学术
万方数据
Liu PF , Xiao L , Chang LB et al. Intervention of blue light with short wavelength on the progression of form deprived myopia in guinea pigs[J]Chin J Exp Ophthalmol 2013,31(10):925-929. DOI: 10.3760/cma.j.issn.2095-0160.2013.10.005 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[5]
Jiang L , Zhang S , Schaeffel F et al. Interactions of chromatic and lens-induced defocus during visual control of eye growth in guinea pigs (Cavia porcellus)[J]Vision Res 2014,94:24-32. DOI: 10.1016/j.visres.2013.10.020 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Rucker FJ . The role of luminance and chromatic cues in emmetropisation[J]Ophthalmic Physiol Opt 2013,33(3):196-214. DOI: 10.1111/opo.12050 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Mandelman T , Sivak JG . Longitudinal chromatic aberration of the vertebrate eye[J]Vision Res 1983,23(12):1555-1559. DOI: 10.1364/josaa.25.002263 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Smith EL 3rd , Hung LF , Arumugam B et al. Effects of long-wavelength lighting on refractive development in infant rhesus monkeys[J]Invest Ophthalmol Vis Sci 2015,56(11):6490-6500. DOI: 10.1167/iovs.15-17025 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Gawne TJ , Siegwart JT Jr, Ward AH et al. The wavelength composition and temporal modulation of ambient lighting strongly affect refractive development in young tree shrews[J]Exp Eye Res 2017,155:75-84. DOI: 10.1016/j.exer.2016.12.004 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Zou L , Zhu X , Liu R et al. Effect of altered retinal cones/opsins on refractive development under monochromatic lights in guinea pigs[J/OL]J Ophthalmol 2018,2018:9197631[2022-09-10]https://pubmed.ncbi.nlm.nih.gov/29675275/. DOI: 10.1155/2018/9197631 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
刘睿邹蕾蕾刘望原. 430 nm和530 nm单色光对豚鼠眼球背侧及腹侧屈光发育的影响[J]中国眼耳鼻喉科杂志 2018,18(3):191-195. DOI: 10.14166/j.issn.1671-2420.2018.03.016 .
返回引文位置Google Scholar
百度学术
万方数据
Liu R , Zou LL , Liu WY et al. Effect of 430 nm and 530 nm wavelength monochromatic light on ocular growth of guinea pig eyes in dorsal and ventral parts[J]Chin J Ophthalmol Otorhinol 2018,18(3):191-195. DOI: 10.14166/j.issn.1671-2420.2018.03.016 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[12]
Li XJ , Yang XP , Wan GM et al. Expression of hepatocyte growth factor and its receptor c-Met in lens-induced myopia in guinea pigs[J]Chin Med J (Engl) 2013,126(23):4524-4527.
返回引文位置Google Scholar
百度学术
万方数据
[13]
Mertz JR , Wallman J Choroidal retinoic acid synthesis:a possible mediator between refractive error and compensatory eye growth[J]Exp Eye Res 2000,70(4):519-527. DOI: 10.1006/exer.1999.0813 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Gan J , Li SM , Atchison DA et al. Association between color vision deficiency and myopia in Chinese children over a five-year period[J/OL]Invest Ophthalmol Vis Sci 2022,63(2):2[2022-09-10]https://pubmed.ncbi.nlm.nih.gov/35103751/. DOI: 10.1167/iovs.63.2.2 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Qian YS , Chu RY , He JC et al. Incidence of myopia in high school students with and without red-green color vision deficiency[J]Invest Ophthalmol Vis Sci 2009,50(4):1598-1605. DOI: 10.1167/iovs.07-1362 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Ostadimoghaddam H , Yekta AA , Heravian J et al. Prevalence of refractive errors in students with and without color vision deficiency[J]J Ophthalmic Vis Res 2014,9(4):484-486. DOI: 10.4103/2008-322X.150828 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Gisbert S , Schaeffel F M to L cone ratios determine eye sizes and baseline refractions in chickens[J]Exp Eye Res 2018,172:104-111. DOI: 10.1016/j.exer.2018.03.029 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Gisbert S , Feldkaemper M , Wahl S et al. Interactions of cone abundancies,opsin expression,and environmental lighting with emmetropization in chickens[J/OL]Exp Eye Res 2020,200:108205[2022-09-11]https://pubmed.ncbi.nlm.nih.gov/32866531/. DOI: 10.1016/j.exer.2020.108205 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Ji S , Mao X , Zhang Y et al. Contribution of M-opsin-based color vision to refractive development in mice[J/OL]Exp Eye Res 2021,209:108669[2022-09-12]https://pubmed.ncbi.nlm.nih.gov/34126082/. DOI: 10.1016/j.exer.2021.108669 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Rucker FJ , Kruger PB . Cone contributions to signals for accommodation and the relationship to refractive error[J]Vision Res 2006,46(19):3079-3089. DOI: 10.1016/j.visres.2006.04.009 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
于曼容戴锦晖视黄酸在实验性近视发生中作用的研究进展[J]中华实验眼科杂志 2017,35(6):552-555. DOI: 10.3760/cma.j.issn.2095-0160.2017.06.014 .
返回引文位置Google Scholar
百度学术
万方数据
Yu MR , Dai JH . Research progress of retinoic acid in experimental myopia[J]Chin J Exp Ophthalmol 2017,35(6):552-555. DOI: 10.3760/cma.j.issn.2095-0160.2017.06.014 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[22]
McFadden SA , Howlett MH , Mertz JR . Retinoic acid signals the direction of ocular elongation in the guinea pig eye[J]Vision Res 2004,44(7):643-653. DOI: 10.1016/j.visres.2003.11.002 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Yu M , Liu W , Wang B et al. Short wavelength (blue) light is protective for lens-induced myopia in guinea pigs potentially through a retinoic acid-related mechanism[J/OL]Invest Ophthalmol Vis Sci 2021,62(1):21[2022-09-13]https://pubmed.ncbi.nlm.nih.gov/33475690/. DOI: 10.1167/iovs.62.1.21 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
McBrien NA , Lawlor P , Gentle A Scleral remodeling during the development of and recovery from axial myopia in the tree shrew[J]Invest Ophthalmol Vis Sci 2000,41(12):3713-3719.
返回引文位置Google Scholar
百度学术
万方数据
[25]
Siegwart JT Jr, Norton TT . Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery[J]Invest Ophthalmol Vis Sci 2005,46(10):3484-3492. DOI: 10.1167/iovs.05-0194 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Bitzer M , Feldkaemper M , Schaeffel F Visually induced changes in components of the retinoic acid system in fundal layers of the chick[J]Exp Eye Res 2000,70(1):97-106. DOI: 10.1006/exer.1999.0762 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
戴锦晖,Email:mocdef.6ab218iuhnijiad
B
刘红,Email:tendef.3ab62fezgnohuil
C

邹蕾蕾和刘睿对本文有同等贡献

D

邹蕾蕾:实施研究、分析数据;刘睿:分析数据及起草文章;刘红:文章知识性内容的审阅和智力性内容的修改;戴锦晖:参与选题、实验指导及文章定稿

E
所有作者均声明不存在利益冲突
F
福建省卫生健康科技计划项目 (2022GGA039)
福建省自然科学基金项目 (2023J011302)
国家自然科学基金项目 (81970831、82070997)
评论 (0条)
注册
登录
时间排序
暂无评论,发表第一条评论抢沙发
MedAI助手(体验版)
文档即答
智问智答
机器翻译
回答内容由人工智能生成,我社无法保证其准确性和完整性,该生成内容不代表我们的态度或观点,仅供参考。
生成快照
文献快照

你好,我可以帮助您更好的了解本文,请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持:

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号