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Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus

Published online by Cambridge University Press:  28 November 2016

YAN ZHANG ,
YUE LIU ,
ABRAHAM HANG ,
EILEEN PHAN  and
CHRISTINE F. WILDSOET
YAN ZHANG*
Affiliation:
Center for Eye Disease & Development, School of Optometry, University of California, Berkeley, CA, USA
YUE LIU
Affiliation:
Center for Eye Disease & Development, School of Optometry, University of California, Berkeley, CA, USA
ABRAHAM HANG
Affiliation:
Center for Eye Disease & Development, School of Optometry, University of California, Berkeley, CA, USA
EILEEN PHAN
Affiliation:
Center for Eye Disease & Development, School of Optometry, University of California, Berkeley, CA, USA
CHRISTINE F. WILDSOET
Affiliation:
Center for Eye Disease & Development, School of Optometry, University of California, Berkeley, CA, USA
*
*Address correspondence to: Yan Zhang, M.D., Ph.D., 588 Minor Hall, School of Optometry, University of California, Berkeley, Berkeley, CA 94720. E-mail: yanzhang@berkeley.edu
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Abstract

Recent studies have demonstrated the defocus sign-dependent, bidirectional gene expression regulation of bone morphogenetic proteins, BMP2, 4 and 7 in chick RPE. In this study, we examined the effects of imposed positive (+10 D) and negative (−10 D) lenses on the gene expression of these BMPs and BMP receptors (BMPR1A, BMPR1B, BMPR2) in chick retina and choroid after monocular lens treatment for 2 or 48 h, as indicators of the roles of retinal and choroidal BMPs and receptors in postnatal eye growth regulation. In retina, although all genes were expressed, neither +10 nor −10 D lenses, worn for either 2 or 48 h, significantly altered gene expression. In contrast, treatment-related differential gene expression was detected in the choroid for both BMPs and their receptors, although interestingly, with the +10 D lens, BMP2 was up-regulated by 156.7 ± 19.7% after 2 h, while BMPR1A was down-regulated to 82.3 ± 12.5% only after 48 h. With the −10 D lens, only the gene expression of BMPR1B was significantly altered, being up-regulated by 162.3 ± 21.2% after 48 h. Untreated birds showed no difference in expression between their two eyes, for any of the genes examined. The finding that retinal gene expression for BMP2, 4, 7 and their receptors are not affected by short-term optical defocus contrasts with previous observations of sign-dependent expression changes for the same genes in the RPE. The latter changes were also larger and more consistent in direction than the choroidal gene expression changes reported here. The interrelationship between these various changes and their biological significance for eye growth regulation are yet to be elucidated.

Keywords

MyopiaBone morphogenetic proteinRetinaChoroid
Type
Research Article
Information
Visual Neuroscience , Volume 33 , 2016 , E015
Copyright
Copyright © Cambridge University Press 2016 

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References

Bakrania, P., Efthymiou, M., Klein, J.C., Salt, A., Bunyan, D.J., Wyatt, A., Ponting, C.P., Martin, A., Williams, S., Lindley, V., Gilmore, J., Restori, M., Robson, A.G., Neveu, M.M., Holder, G.E., Collin, J.R., Robinson, D.O., Farndon, P., Johansen-Berg, H., Gerrelli, D. & Ragge, N.K. (2008). Mutations in BMP4 cause eye, brain, and digit developmental anomalies: Overlap between the BMP4 and hedgehog signaling pathways. The American Journal of Human Genetics 82, 304–319.CrossRefGoogle ScholarPubMed
Crewther, D.P. (2000). The role of photoreceptors in the control of refractive state. Progress in Retinal and Eye Research 19, 421–457.CrossRefGoogle ScholarPubMed
Cui, W., Bryant, M.R., Sweet, P.M. & McDonnell, P.J. (2004). Changes in gene expression in response to mechanical strain in human scleral fibroblasts. Experimental Eye Research 78, 275–284.Google Scholar
Dolgin, E. (2015). The myopia boom. Nature 519, 276–278.CrossRefGoogle ScholarPubMed
Flitcroft, D.I. (2013). Is myopia a failure of homeostasis? Experimental Eye Research 114, 16–24.Google Scholar
He, L., Frost, M.R., Siegwart, J.T. Jr. & Norton, T.T. (2014a). Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery. Experimental Eye Research 123, 56–71.CrossRefGoogle ScholarPubMed
He, L., Frost, M.R., Siegwart, J.T. Jr. & Norton, T.T. (2014b). Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions. Vision Research 102, 52–63.Google Scholar
Hu, J., Cui, D., Yang, X., Wang, S., Hu, S., Li, C. & Zeng, J. (2008). Bone morphogenetic protein-2: A potential regulator in scleral remodeling. Molecular Vision 14, 2373–2380.Google ScholarPubMed
Li, H., Cui, D., Zhao, F., Huo, L., Hu, J. & Zeng, J. (2015). BMP-2 is involved in scleral remodeling in myopia development. PloS One 10, e0125219.CrossRefGoogle ScholarPubMed
Maminishkis, A., Chen, S., Jalickee, S., Banzon, T., Shi, G., Wang, F.E., Ehalt, T., Hammer, J.A. & Miller, S.S. (2006). Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue. Investigative Opthalmology & Visual Science 47, 3612–3624.Google Scholar
McGlinn, A.M., Baldwin, D.A., Tobias, J.W., Budak, M.T., Khurana, T.S. & Stone, R.A. (2007). Form-deprivation myopia in chick induces limited changes in retinal gene expression. Investigative Opthalmology & Visual Science 48, 3430–3436.CrossRefGoogle ScholarPubMed
Morgan, I.G., Ashby, R.S. & Nickla, D.L. (2013). Form deprivation and lens-induced myopia: Are they different? Ophthalmic and Physiological Optics 33, 355–361.Google Scholar
Nickla, D.L. & Totonelly, K. (2011). Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia. Experimental Eye Research 93, 782–785.Google Scholar
Nickla, D.L. & Wallman, J. (2010). The multifunctional choroid. Progress in Retinal and Eye Research 29, 144–168.CrossRefGoogle ScholarPubMed
Rada, J.A., Shelton, S. & Norton, T.T. (2006). The sclera and myopia. Experimental Eye Research 82, 185–200.Google Scholar
Rymer, J. & Wildsoet, C.F. (2005). The role of the retinal pigment epithelium in eye growth regulation and myopia: A review. Visual Neuroscience 22, 251–261.CrossRefGoogle ScholarPubMed
Troilo, D., Gottlieb, M.D. & Wallman, J. (1987). Visual deprivation causes myopia in chicks with optic nerve section. Current Eye Research 6, 993–999.Google Scholar
Verhoeven, V.J., Hysi, P.G., Wojciechowski, R., Fan, Q., Guggenheim, J.A., Höhn, R., MacGregor, S., Hewitt, A.W., Nag, A., Cheng, C.Y., Yonova-Doing, E., Zhou, X., Ikram, M.K., Buitendijk, G.H., McMahon, G., Kemp, J.P., Pourcain, B.S., Simpson, C.L., Mäkelä, K.M., Lehtimäki, T., Kähönen, M., Paterson, A.D., Hosseini, S.M., Wong, H.S., Xu, L., Jonas, J.B., Pärssinen, O., Wedenoja, J., Yip, S.P., Ho, D.W., Pang, C.P., Chen, L.J., Burdon, K.P., Craig, J.E., Klein, B.E., Klein, R., Haller, T., Metspalu, A., Khor, C.C., Tai, E.S., Aung, T., Vithana, E., Tay, W.T., Barathi, V.A., Consortium for Refractive Error and Myopia (CREAM), Chen, P., Li, R., Liao, J., Zheng, Y., Ong, R.T., Döring, A.; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Evans, D.M., Timpson, N.J., Verkerk, A.J., Meitinger, T., Raitakari, O., Hawthorne, F., Spector, T.D., Karssen, L.C., Pirastu, M., Murgia, F., Ang, W.; Wellcome Trust Case Control Consortium 2 (WTCCC2), Mishra, A., Montgomery, G.W., Pennell, C.E., Cumberland, P.M., Cotlarciuc, I., Mitchell, P., Wang, J.J., Schache, M., Janmahasatian, S., Igo, R.P. Jr., Lass, J.H., Chew, E., Iyengar, S.K.; Fuchs’ Genetics Multi-Center Study Group, Gorgels, T.G., Rudan, I., Hayward, C., Wright, A.F., Polasek, O., Vatavuk, Z., Wilson, J.F., Fleck, B., Zeller, T., Mirshahi, A., Müller, C., Uitterlinden, A.G., Rivadeneira, F., Vingerling, J.R., Hofman, A., Oostra, B.A., Amin, N., Bergen, A.A., Teo, Y.Y., Rahi, J.S., Vitart, V., Williams, C., Baird, P.N., Wong, T.Y., Oexle, K., Pfeiffer, N., Mackey, D.A., Young, T.L., van Duijn, C.M., Saw, S.M., Bailey-Wilson, J.E., Stambolian, D., Klaver, C.C. & Hammond, C.J. (2013). Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics 45, 314–318.CrossRefGoogle ScholarPubMed
Vitale, S., Sperduto, R.D. & Ferris, F.L. III. (2009). Increased prevalence of myopia in the United States between 1971–1972 and 1999–2004. Archives of Ophthalmology 127, 1632–1639.Google Scholar
Wallman, J. & Winawer, J. (2004). Homeostasis of eye growth and the question of myopia. Neuron 43, 447–468.Google Scholar
Wang, Q., Zhao, G., Xing, S., Zhang, L. & Yang, X. (2011). Role of bone morphogenetic proteins in form-deprivation myopia sclera. Molecular Vision 17, 647–657.Google Scholar
Wang, Q., Xue, M.L., Zhao, G.Q., Liu, M.G., Ma, Y.N. & Ma, Y. (2015). Form-deprivation myopia induces decreased expression of bone morphogenetic protein-2, 5 in Guinea pig sclera. International Journal of Ophthalmology 8, 39–45.Google ScholarPubMed
Wiesel, T.N. & Raviola, E. (1977). Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature 266, 66–68.Google Scholar
Wildsoet, C. & Wallman, J. (1995). Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Research 35, 1175–1194.Google Scholar
Wildsoet, C. (2003). Neural pathways subserving negative lens-induced emmetropization in chicks–insights from selective lesions of the optic nerve and ciliary nerve. Current Eye Research 27, 371–385.Google Scholar
Wojciechowski, R. (2011). Nature and nurture: The complex genetics of myopia and refractive error. Clinical Genetics 79, 301–320.CrossRefGoogle ScholarPubMed
Zhang, Y., Liu, Y. & Wildsoet, C.F. (2012). Bidirectional, optical sign-dependent regulation of BMP2 gene expression in chick retinal pigment epithelium. Investigative Opthalmology & Visual Science 53, 6072–6080.Google Scholar
Zhang, Y., Liu, Y., Ho, C. & Wildsoet, C.F. (2013). Effects of imposed defocus of opposite sign on temporal gene expression patterns of BMP4 and BMP7 in chick RPE. Experimental Eye Research 109, 98–106.Google Scholar
Zhang, Y. & Wildsoet, C.F. (2015). RPE and choroid mechanisms underlying ocular growth and myopia. Progress in Molecular Biology and Translational Science 134, 221–240.Google Scholar
Zhang, Y., Raychaudhuri, S. & Wildsoet, C.F. (2016). Imposed optical defocus induces isoform-specific up-regulation of TGFbeta gene expression in chick retinal pigment epithelium and choroid but not neural retina. PloS One 11 e0155356.Google Scholar