https://doi.org/10.4081/ejh.2024.3982
Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs
Submitted: 31 January 2024
Accepted: 17 May 2024
Published: 27 June 2024
Accepted: 17 May 2024
Abstract Views: 579
PDF: 206
HTML: 10
HTML: 10
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.
Rudnicka AR, Kapetanakis VV, Wathern AK, Logan NS, Gilmartin B, Whincup PH, et al. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention. Br J Ophthalmol 2016;100:882-90.
DOI: https://doi.org/10.1136/bjophthalmol-2015-307724
Flitcroft DI, He M, Jonas JB, Jong M, Naidoo K, Ohno-Matsui K, et al. IMI-defining and classifying myopia: a proposed set of standards for clinical and epidemiologic studies. Invest Ophthalmol Vis Sci 2019;60:M20-30.
DOI: https://doi.org/10.1167/iovs.18-25957
Morgan IG, Ashby RS. Bright light blocks the development of form deprivation myopia in mice, acting on d1 dopamine receptors. Invest Ophthalmol Vis Sci 2017;58:2317.
DOI: https://doi.org/10.1167/iovs.17-21871
4.Torii H, Kurihara T, Seko Y, Negishi K, Ohnuma K, Inaba T, et al. Violet light exposure can be a preventive strategy against myopia progression. EBioMedicine 2017;15:210-9.
DOI: https://doi.org/10.1016/j.ebiom.2016.12.007
Prepas SB. Light, literacy and the absence of ultraviolet radiation in the development of myopia. Med Hypotheses 2008;70:635-7.
DOI: https://doi.org/10.1016/j.mehy.2007.07.023
Kröger RH, Binder S. Use of paper selectively absorbing long wavelengths to reduce the impact of educational near work on human refractive development. Br J Ophthalmol 2000;84:890-3.
DOI: https://doi.org/10.1136/bjo.84.8.890
Wang F, Zhou J, Lu Y, Chu R. Effects of 530 nm green light on refractive status, melatonin, MT1 receptor, and melanopsin in the guinea pig. Curr Eye Res 2011;36:103-11.
DOI: https://doi.org/10.3109/02713683.2010.526750
Foulds WS, Barathi VA, Luu CD. Progressive myopia or hyperopia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light. Invest Ophthalmol Vis Sci 2013;54:8004-12.
DOI: https://doi.org/10.1167/iovs.13-12476
Jiang L, Zhang S, Schaeffel F, Xiong S, Zheng Y, Zhou X, et al. Interactions of chromatic and lens-induced defocus during visual control of eye growth in guinea pigs (Cavia porcellus). Vision Res 2014;94:24-32.
DOI: https://doi.org/10.1016/j.visres.2013.10.020
Hung LF, Arumugam B, She Z, Ostrin L, Smith EL. Narrowband, long-wavelength lighting promotes hyperopia and retards vision-induced myopia in infant rhesus monkeys. Exp Eye Res 2018;176:147-60.
DOI: https://doi.org/10.1016/j.exer.2018.07.004
Smith EL III, Hung LF, Arumugam B, Holden BA, Neitz M, Neitz J. Effects of long-wavelength lighting on refractive development in infant rhesus monkeys. Invest Ophthalmol Vis Sci 2015;56:6490-500.
DOI: https://doi.org/10.1167/iovs.15-17025
Gawne TJ, Siegwart JT Jr, Ward AH, Norton TT. The wavelength composition and temporal modulation of ambient lighting strongly affect refractive development in young tree shrews. Exp Eye Res 2017;155:75-84.
DOI: https://doi.org/10.1016/j.exer.2016.12.004
Wu PC, Chen CT, Lin KK, Sun CC, Kuo CN, Huang HM, et al. Myopia prevention and outdoor light intensity in a school-based cluster randomized Trial. Ophthalmology 2018;125:1239-50.
DOI: https://doi.org/10.1016/j.ophtha.2017.12.011
He M, Xiang F, Zeng Y, Mai J, Chen Q, Zhang J, et al. Effect of time spent outdoors at school on the development of myopia among children in China: A randomized clinical trial. JAMA 2015;314:1142-8.
DOI: https://doi.org/10.1001/jama.2015.10803
Zadnik K, Mutti DO. Outdoor activity protects against childhood myopia-let the sun shine in. JAMA Pediatr 2019;173:415-6.
DOI: https://doi.org/10.1001/jamapediatrics.2019.0278
Sherwin JC, Reacher MH, Keogh RH, Khawaja AP, Mackey DA, Foster PJ. The association between time spent outdoors and myopia in children and adolescents: a systematic review and meta-analysis. Ophthalmology 2012;119:2141-51.
DOI: https://doi.org/10.1016/j.ophtha.2012.04.020
Saw SM, Zhang MZ, Hong RZ, Fu ZF, Pang MH, Tan DT. Near-work activity, night-lights, and myopia in the Singapore-China study. Arch Ophthalmol 2002;120:620-7.
DOI: https://doi.org/10.1001/archopht.120.5.620
Tideman JWL, Polling JR, Jaddoe VWV, Vingerling JR, Klaver CCW. Environmental risk factors can reduce axial length elongation and myopia incidence in 6-to 9-year-old children. Ophthalmology 2019;126:127-36.
DOI: https://doi.org/10.1016/j.ophtha.2018.06.029
Karuppiah V, Wong L, Tay V, Ge X, Kang LL. School-based programme to address childhood myopia in Singapore. Singapore Med J 2021;62:63-8.
DOI: https://doi.org/10.11622/smedj.2019144
Li W, Lan W, Yang S, Liao Y, Xu Q, Lin L, et al. The effect of spectral property and intensity of light on natural refractive development and compensation to negative lenses in guinea pigs. Invest Ophthalmol Vis Sci 2014;55:6324-32.
DOI: https://doi.org/10.1167/iovs.13-13802
Zhang CW, Xu JH, Wang YL, Xu W, Li K. Survey and analysis of visual acuity of Kazakhs in different lighting environments. Genet Mol Res 2014;13:2451-7.
DOI: https://doi.org/10.4238/2014.April.3.17
Xu X, Shi J, Zhang C, Shi L, Bai Y, Shi W, Wang Y. Effects of artificial light with different spectral composition on eye axial growth in juvenile guinea pigs. Eur J Histochem 2023;67:3634.
DOI: https://doi.org/10.4081/ejh.2023.3634
Liu Y, Wang YL, Wang KL, Liu F, Zong X. Influence of artificial luminous environment and TCM intervention on development of myopia rabbits. Asian Pac J Trop Med 2015;8:243-8.
DOI: https://doi.org/10.1016/S1995-7645(14)60325-4
Garcia MB, Jha AK, Healy KE, Wildsoet CF. A bioengineering approach to myopia control tested in a Guinea pig model. Invest Ophthalmol Vis Sci 2017;58:1875-86.
DOI: https://doi.org/10.1167/iovs.16-20694
Rada JA, Johnson JM, Achen VR, Rada KG. Inhibition of scleral proteoglycan synthesis blocks deprivation-induced axial elongation in chicks. Exp Eye Res 2002;74:205-15.
DOI: https://doi.org/10.1006/exer.2001.1113
McBrien NA, Gentle A. The role of visual information in the control of scleral matrix biology in myopia. Curr Eye Res 2001;23:313-9.
DOI: https://doi.org/10.1076/ceyr.23.5.313.5440
Wildsoet C, Wallman J. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res 1995;35:1175-94.
DOI: https://doi.org/10.1016/0042-6989(94)00233-C
Zhu X, Winawer JA, Wallman J. Potency of myopic defocus in spectacle lens compensation. Invest Ophthalmol Vis Sci 2003;44:2818-27.
DOI: https://doi.org/10.1167/iovs.02-0606
Zhao F, Zhou Q, Reinach PS, Yang J, Ma L, Wang X, et al. Cause and effect relationship between changes in scleral matrix metallopeptidase-2 expression and myopia Development in mice. Am J Pathol 2018;188:1754-67.
DOI: https://doi.org/10.1016/j.ajpath.2018.04.011
Liu YX, Sun Y. MMP-2 participates in the sclera of guinea pig with form-deprivation myopia via IGF-1/STAT3 pathway. Eur Rev Med Pharmacol Sci 2018;22:2541-48.
Chen M, Qian Y, Dai J, Chu R. The sonic hedgehog signaling pathway induces myopic development by activating matrix metalloproteinase (MMP)-2 in Guinea pigs. PLoS One 2014;9:e96952.
DOI: https://doi.org/10.1371/journal.pone.0096952
Oh DJ, Martin JL, Williams AJ, Peck RE, Pokorny C, Russell P, et al. Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost. Invest Ophthalmol Vis Sci 2006;47:953-63.
DOI: https://doi.org/10.1167/iovs.05-0516
Downie LE, Busija L, Keller PR. Blue-light filtering intraocular lenses (IOLs) for protecting macular health. Cochrane Database Syst Rev 2018;5:CD011977.
DOI: https://doi.org/10.1002/14651858.CD011977.pub2
Muralidharan AR, Low SWY, Lee YC, Barathi VA, Saw SM, Milea D, et al. Recovery from form-deprivation myopia in chicks is dependent upon the fullness and correlated color temperature of the light spectrum. Invest Ophthalmol Vis Sci 2022;63:16.
DOI: https://doi.org/10.1167/iovs.63.2.16
Hu YZ, Yang H, Li H, Lv LB, Wu J, Zhu Z, et al. Low color temperature artificial lighting can slow myopia development: long-term study using juvenile monkeys. Zool Res 2022;43:229-33.
DOI: https://doi.org/10.21203/rs.3.rs-952597/v1
Seidemann A, Schaeffel F. Effects of longitudinal chromatic aberration on accommodation and emmetropization. Vision Res 2002;42:2409-17.
DOI: https://doi.org/10.1016/S0042-6989(02)00262-6
Hannibal J, Georg B, Fahrenkrug J. Differential expression of melanopsin mRNA and protein in brown Norwegian rats. Exp Eye Res 2013;106:55-63.
DOI: https://doi.org/10.1016/j.exer.2012.11.006
Liu AL, Liu YF, Wang G, Shao YQ, Yu CX, Yang Z, et al. The role of ipRGCs in ocular growth and myopia development. Sci Adv 2022;8:eabm9027.
DOI: https://doi.org/10.1126/sciadv.abm9027
Chakraborty R, Landis EG, Mazade R, Yang V, Strickland R, Hattar S, et al. Melanopsin modulates refractive development and myopia. Exp Eye Res 2022;214:108866.
DOI: https://doi.org/10.1016/j.exer.2021.108866
Osborne NN, Núñez-Álvarez C, Del Olmo-Aguado S, Merrayo-Lloves J. Visual light effects on mitochondria: The potential implications in relation to glaucoma. Mitochondrion 2017;36:29-35.
DOI: https://doi.org/10.1016/j.mito.2016.11.009
Xiao H, Fan ZY, Tian XD, Xu YC. Comparison of form-deprived myopia and lens-induced myopia in guinea pigs. Int J Ophthalmol 2014;7:245-50.
Singh SE, Wildsoet CF, Roorda AJ. Optical aberrations of guinea pig eyes. Invest Ophthalmol Vis Sci 2020;61:39.
DOI: https://doi.org/10.1167/iovs.61.10.39
Gottlieb MD, Joshi HB, Nickla DL. Scleral changes in chicks with form-deprivation myopia. Curr Eye Res 1990;9:1157-65.
DOI: https://doi.org/10.3109/02713689009003472
Murata K, Hirata A, Ohta K, Enaida H, Nakamura KI. Morphometric analysis in mouse scleral fibroblasts using focused ion beam/scanning electron microscopy. Sci Rep 2019;9:6329.
DOI: https://doi.org/10.1038/s41598-019-42758-x
McBrien NA, Cornell LM, Gentle A. Structural and ultrastructural changes to the sclera in a mammalian model of high myopia. Invest Ophthalmol Vis Sci 2001;42:2179-87.
Wu H, Chen W, Zhao F, Zhou Q, Reinach PS, Deng L, et al. Scleral hypoxia is a target for myopia control. Proc Natl Acad Sci USA 2018;115:E7091-100.
DOI: https://doi.org/10.1073/pnas.1721443115
Siegwart JT Jr, Norton TT. The time course of changes in mRNA levels in tree shrews clera during induced myopia and recovery. Invest Ophthalmol Vis Sci 2002;43:2067-75.
Siegwart JT Jr, Norton TT. Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery. Invest Ophthalmol Vis Sci 2005;46:3484-92.
DOI: https://doi.org/10.1167/iovs.05-0194
Schippert R, Brand C, Schaeffel F, Feldkaemper MP. Changes in scleral MMP-2, TIMP-2 and TGFbeta-2 mRNA expression after imposed myopic and hyperopic defocus in chickens. Exp Eye Res 2006;82:710-9.
DOI: https://doi.org/10.1016/j.exer.2005.09.010
Jia Y, Hu DN, Sun J, Zhou JB．Correlations between MMPs and TIMPs levels in aqueous humor from high myopia and cataract patients. Curr Eye Res 2017;42:600-3.
DOI: https://doi.org/10.1080/02713683.2016.1223317
Guggenheim JA, McBien NA. Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew. Invest Ophthalmol Vis Sci 1996;37:1380-95.
Rada JA, Brenza HL. Increased latent gelatinase activity in the sclera of visually deprived chicks. Invest Ophthalmol Vis Sci 1995;36:1555-65.
Liu HH, Kenning MS, Jobling AI, McBrien NA, Gentle A. Reduced scleral TIMP-2 expression is associated with myopia development: TIMP-2 supplementation stabilizes scleral biomarkers of myopia and limits myopia development. Invest Ophthalmol Vis Sci 2017;58:1971-81.
DOI: https://doi.org/10.1167/iovs.16-21181
Giannelli G, Bergamini C, Marinosci F, Fransvea E, Quaranta M, Lupo L, et al. Clinical role of MMP-2/TIMP-2 imbalance in hepatocellular carcinoma. Int J Cancer 2002;97:425-31.
DOI: https://doi.org/10.1002/ijc.1635
Fan YZ, Zhang JT, Yang HC, Yang YQ. Expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 in gallbladder carcinoma and their significance. World J Gastroenterol 2002;8:1138-43.
DOI: https://doi.org/10.3748/wjg.v8.i6.1138
Xu K, Hou S, Du Z. Prognostic value of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in bladder carcinoma. Chin Med J (Engl) 2002;115:743-5.
Ethics Approval
this study was approved by the Animal Care and Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese MedicineSupporting Agencies
National Nature Science Foundation of China , Jiangsu Health Vocational CollegeHow to Cite
Yuan, J., Li, L., Fan, Y., Xu, X., Huang, X., Shi, J., … Wang, Y. (2024). Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.3982
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Fengqin Yan, Hong Zhu, Yingxia He, Qinqin Wu, Xiaoyu Duan, Combination of tolvaptan and valsartan improves cardiac and renal functions in doxorubicin-induced heart failure in mice , European Journal of Histochemistry: Vol. 66 No. 4 (2022)
- Kazuhiko Hashimoto, Shunji Nishimura, Yu Shinyashiki, Tomohiko Ito, Ryosuke Kakinoki, Masao Akagi, Clinicopathological assessment of PD-1/PD-L1 immune checkpoint expression in desmoid tumors , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
1
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
147
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
