Hostname: page-component-848d4c4894-xfwgj Total loading time: 0 Render date: 2024-06-26T20:12:25.387Z Has data issue: false hasContentIssue false
  • English
  • Français

Mechanisms for persistent microphthalmia following ethanol exposure during retinal neurogenesis in zebrafish embryos

Published online by Cambridge University Press:  20 July 2007

BHAVANI KASHYAP ,
LOGAN C. FREDERICKSON  and
DEBORAH L. STENKAMP
BHAVANI KASHYAP
Affiliation:
Department of Biological Sciences, and Neuroscience Graduate Program, University of Idaho, Moscow, Idaho
LOGAN C. FREDERICKSON
Affiliation:
Department of Biological Sciences, and Neuroscience Graduate Program, University of Idaho, Moscow, Idaho
DEBORAH L. STENKAMP
Affiliation:
Department of Biological Sciences, and Neuroscience Graduate Program, University of Idaho, Moscow, Idaho
Get access Rights & Permissions [Opens in a new window]

Abstract

The exposure of the developing human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the visual system. One common phenotype seen in humans exposed to ethanol in utero is microphthalmia. The objective of this study was to describe the effects of ethanol during retinal neurogenesis in a model organism, the zebrafish, and to pursue the potential mechanisms by which ethanol causes microphthalmia. Zebrafish embryos were exposed to 1% or 1.5% ethanol from 24 to 48 h after fertilization, a period during which the retinal neuroepithelium undergoes rapid proliferation and differentiation to form a laminated structure composed of different retinal cell types. Ethanol exposure resulted in significantly reduced eye size immediately following the treatment, and this microphthalmia persisted through larval development. This reduced eye size could not entirely be accounted for by the accompanying general delay in embryonic development. Retinal cell death was only slightly higher in ethanol-exposed embryos, although cell death in the lens was extensive in some of these embryos, and lenses were significantly reduced in size as compared to those of control embryos. The initiation of retinal neurogenesis was not affected, but the subsequent waves of cell differentiation were markedly reduced. Even cells that were likely generated after ethanol exposure—rod and cone photoreceptors and Müller glia—were delayed in their expression of cell-specific markers by at least 24 h. We conclude that ethanol exposure over the time of retinal neurogenesis resulted in persistent microphthalmia due to a combination of an overall developmental delay, lens abnormalities, and reduced retinal cell differentiation.

Keywords

MicrophthalmiaEthanolRetinaNeurogenesisFetal Alcohol Syndrome
Type
Research Article
Information
Visual Neuroscience , Volume 24 , Issue 3 , May 2007 , pp. 409 - 421
Copyright
© 2007 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ahlgren, S.C., Thakur, V. & Bronner-Fraser, M. (2002). Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proceedings of the National Academy of Sciences 99, 10476–10481.Google Scholar
Arenzana, F.J., Carvan, M.J., 3rd, Aijon, J., Sanchez-Gonzalez, R., Arevalo, R. & Porteros, A. (2006). Teratogenic effects of ethanol exposure on zebrafish visual system development. Neurotoxicology and Teratology 28, 342–348.Google Scholar
Barthel, L.K. & Raymond, P.A. (1993). Subcellular localization of alpha-tubulin and opsin mRNA in the goldfish retina using digoxigenin-labeled cRNA probes detected by alkaline phosphatase and HRP histochemistry. Journal of Neuroscience Methods 50, 145–152.Google Scholar
Biehlmaier, O., Neuhauss, S.C. & Kohler, K. (2001). Onset and time course of apoptosis in the developing zebrafish retina. Cell Tissue Research 306, 199–207.Google Scholar
Bilotta, J., Barnett, J.A., Hancock, L. & Saszik, S. (2004). Ethanol exposure alters zebrafish development: A novel model of fetal alcohol syndrome. Neurotoxicology and Teratology 26, 737–743.Google Scholar
Bilotta, J., Saszik, S., Givin, C.M., Hardesty, H.R. & Sutherland, S.E. (2002). Effects of embryonic exposure to ethanol on zebrafish visual function. Neurotoxicology and Teratology 24, 759–766.Google Scholar
Blader, P. & Strahle, U. (1998). Ethanol impairs migration of the prechordal plate in the zebrafish embryo. Developmental Biology 201, 185–201.Google Scholar
Bradfield, J.Y., West, J.R. & Maier, S.E. (2006). Uptake and elimination of ethanol by young zebrafish embryos. Neurotoxicology and Teratology 28, 629–633.Google Scholar
Carvan, M.J., 3rd, Loucks, E., Weber, D.N. & Williams, F.E. (2004). Ethanol effects on the developing zebrafish: Neurobehavior and skeletal morphogenesis. Neurotoxicol Teratol 26, 757–768.Google Scholar
Chen, S., Wang, Q.L., Nie, Z., Sun, H., Lennon, G., Copeland, N.G., Gilbert, D.J., Jenkins, N.A. & Zack, D.J. (1997). Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 19, 1017–1030.Google Scholar
Cole, L.K. & Ross, L.S. (2001). Apoptosis in the developing zebrafish embryo. Developmental Biology 240, 123–142.Google Scholar
DeJonge, M.H. & Zachman, R.D. (1995). The effect of maternal ethanol ingestion on fetal rat heart vitamin A: A model for fetal alcohol syndrome. Pediatric Research 37, 418–423.Google Scholar
Deltour, L., Ang, H.L. & Duester, G. (1996). Ethanol inhibition of retinoic acid synthesis as a potential mechanism for fetal alcohol syndrome. The FASEB Journal 10, 1050–1057.Google Scholar
Duester, G. (1991). A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step. Alcoholism: Clinical and Experimental Research 15, 568–572.Google Scholar
Easter, S.S., Jr. & Malicki, J.J. (2002). The zebrafish eye: Developmental and genetic analysis. Results and Problems in Cell Differentiation 40, 346–370.Google Scholar
Edwards, M.J. (1998). Apoptosis, the heat shock response, hyperthermia, birth defects, disease and cancer. Where are the common links? Cell Stress Chaperones 3, 213–220.Google Scholar
Galli-Resta, L., Resta, G., Tan, S.S. & Reese, B.E. (1997). Mosaics of islet-1-expressing amacrine cells assembled by short-range cellular interactions. Journal of Neuroscience 17, 7831–7838.Google Scholar
Han, C.L., Liao, C.S., Wu, C.W., Hwong, C.L., Lee, A.R. & Yin, S.J. (1998). Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family—Implications for etiology of fetal alcohol syndrome and alcohol-related diseases. Europen Journal of Biochemistry 254, 25–31.Google Scholar
Hitchcock, P. & Kakuk-Atkins, L. (2004). The basic helix-loop-helix transcription factor neuroD is expressed in the rod lineage of the teleost retina. Journal of Comparative Neurology 477, 108–117.Google Scholar
Hitchcock, P.F., Macdonald, R.E., VanDeRyt, J.T. & Wilson, S.W. (1996). Antibodies against Pax6 immunostain amacrine and ganglion cells and neuronal progenitors, but not rod precursors, in the normal and regenerating retina of the goldfish. Journal of Neurobiology 29, 399–413.Google Scholar
Hu, M. & Easter, S.S. (1999). Retinal neurogenesis: The formation of the initial central patch of postmitotic cells. Developmental Biology 207, 309–321.Google Scholar
Hug, T.E., Fitzgerald, K.M. & Cibis, G.W. (2000). Clinical and electroretinographic findings in fetal alcohol syndrome. American Association for Pediatric Ophthalmology and Strabismus 4, 200–204.Google Scholar
Hyatt, G.A., Schmitt, E.A., Fadool, J.M. & Dowling, J.E. (1996). Retinoic acid alters photoreceptor development in vivo. Proceedings of the National Academy of Sciences 93, 13298–13303.Google Scholar
Hyer, J., Kuhlman, J., Afif, E. & Mikawa, T. (2003). Optic cup morphogenesis requires pre-lens ectoderm but not lens differentiation. Developmental Biology 259, 351–363.Google Scholar
Ikonomidou, C., Bittigau, P., Ishimaru, M.J., Wozniak, D.F., Koch, C., Genz, K., Price, M.T., Stefovska, V., Horster, F., Tenkova, T., Dikranian, K. & Olney, J.W. (2000). Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287, 1056–1060.Google Scholar
Jones, K.L. & Smith, D.W. (1973). Recognition of the fetal alcohol syndrome in early infancy. Lancet 2, 999–1001.Google Scholar
Kay, J.N., Finger-Baier, K.C., Roeser, T., Staub, W. & Baier, H. (2001). Retinal ganglion cell genesis requires lakritz, a Zebrafish atonal Homolog. Neuron 30, 725–736.Google Scholar
Kelley, M.W., Turner, J.K. & Reh, T.A. (1994). Retinoic acid promotes differentiation of photoreceptors in vitro. Development 120, 2091–2102.Google Scholar
Kim, C.H., Ueshima, E., Muraoka, O., Tanaka, H., Yeo, S.Y., Huh, T.L. & Miki, N. (1996). Zebrafish elav/HuC homologue as a very early neuronal marker. Neuroscience Letters 216, 109–112.Google Scholar
Kimura, A., Singh, D., Wawrousek, E.F., Kikuchi, M., Nakamura, M. & Shinohara, T. (2000). Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression. Journal of Biological Chemistry 275, 1152–1160.Google Scholar
Korzh, V., Sleptsova, I., Liao, J., He, J. & Gong, Z. (1998). Expression of zebrafish bHLH genes ngn1 and nrd defines distinct stages of neural differentiation. Developmental Dynamics 213, 92–104.Google Scholar
Krone, P.H., Evans, T.G. & Blechinger, S.R. (2003). Heat shock gene expression and function during zebrafish embryogenesis. Seminars in Cell and Developmental Biology 14, 267–274.Google Scholar
Larison, K.D. & Bremiller, R. (1990). Early onset of phenotype and cell patterning in the embryonic zebrafish retina. Development 109, 567–576.Google Scholar
Lele, Z., Engel, S. & Krone, P.H. (1997). hsp47 and hsp70 gene expression is differentially regulated in a stress- and tissue-specific manner in zebrafish embryos. Developmental Genet 21, 123–133.Google Scholar
Li, Z., Hu, M., Ochocinska, M.J., Joseph, N.M. & Easter, S.S., Jr. (2000a). Modulation of cell proliferation in the embryonic retina of zebrafish (Danio rerio). Developmental Dynamics 219, 391–401.Google Scholar
Li, Z., Joseph, N.M. & Easter, S.S., Jr. (2000b). The morphogenesis of the zebrafish eye, including a fate map of the optic vesicle. Developmental Dynamics 218, 175–188.Google Scholar
Loucks, E. & Carvan, M.J., 3rd. (2004). Strain-dependent effects of developmental ethanol exposure in zebrafish. Neurotoxicology and Teratology 26, 745–755.Google Scholar
Malicki, J., Neuhauss, S.C., Schier, A.F., Solnica-Krezel, L., Stemple, D.L., Stainier, D.Y., Abdelilah, S., Zwartkruis, F., Rangini, Z. & Driever, W. (1996). Mutations affecting development of the zebrafish retina. Development 123, 263–273.Google Scholar
Marsh-Armstrong, N., McCaffery, P., Gilbert, W., Dowling, J.E. & Drager, U.C. (1994). Retinoic acid is necessary for development of the ventral retina in zebrafish. Proceedings of the National Academy of Sciences 91, 7286–7290.Google Scholar
Masai, I., Stemple, D.L., Okamoto, H. & Wilson, S.W. (2000). Midline signals regulate retinal neurogenesis in zebrafish. Neuron 27, 251–263.Google Scholar
Matsui, J.I., Egana, A.L., Sponholtz, T.R., Adolph, A.R. & Dowling, J.E. (2006). Effects of ethanol on photoreceptors and visual function in developing zebrafish. Investigative Ophthalmology & Visual Science 47, 4589–4597.Google Scholar
Neumann, C.J. & Nuesslein-Volhard, C. (2000). Patterning of the zebrafish retina by a wave of sonic hedgehog activity. Science 289, 2137–2139.Google Scholar
Nornes, S., Clarkson, M., Mikkola, I., Pedersen, M., Bardsley, A., Martinez, J.P., Krauss, S. & Johansen, T. (1998). Zebrafish contains two pax6 genes involved in eye development. Mechanisms of Development 77, 185–196.Google Scholar
Otteson, D.C. & Hitchcock, P.F. (2003). Stem cells in the teleost retina: Persistent neurogenesis and injury-induced regeneration. Vision Research 43, 927–936.Google Scholar
Peng, Y., Yang, P.H., Ng, S.S., Wong, O.G., Liu, J., He, M.L., Kung, H.F. & Lin, M.C. (2004). A critical role of Pax6 in alcohol-induced fetal microcephaly. Neurobiology of Disease 16, 370–376.Google Scholar
Peterson, R.E., Fadool, J.M., McClintock, J. & Linser, P.J. (2001). Muller cell differentiation in the zebrafish neural retina: Evidence of distinct early and late stages in cell maturation. The Journal of Comparative Neurology 429, 530–540.Google Scholar
Pinazo-Duran, M.D., Cervera, R., Pons, S., Zanon-Moreno, V.C., Gallego-Pinazo, R. & Guerri, C. (2005). [Mechanisms of protein expression in the rat optic nerve. Modifications by alcohol exposure]. Archivos de la Sociedad Española de Oftalmología 80, 99–104.Google Scholar
Prabhudesai, S.N., Cameron, D.A. & Stenkamp, D.L. (2005). Targeted effects of retinoic acid signaling upon photoreceptor development in zebrafish. Developmental Biology 287, 157–167.Google Scholar
R, D.C.T. (2006). R: A language and environment for statistical computing. R Foundation for statistical computing, Vienna, Austria.
Raymond, P.A., Barthel, L.K. & Curran, G.A. (1995). Developmental patterning of rod and cone photoreceptors in embryonic zebrafish. The Journal of Comparative Neurology 359, 537–550.Google Scholar
Reimers, M.J., La Du, J.K., Periera, C.B., Giovanini, J. & Tanguay, R.L. (2006). Ethanol-dependent toxicity in zebrafish is partially attenuated by antioxidants. Neurotoxicology and Teratology 28, 497–508.Google Scholar
Rojas-Munoz, A., Dahm, R. & Nusslein-Volhard, C. (2005). chokh/rx3 specifies the retinal pigment epithelium fate independently of eye morphogenesis. Developmental Biology 288, 348–362.Google Scholar
Schmitt, E.A. & Dowling, J.E. (1996). Comparison of topographical patterns of ganglion and photoreceptor cell differentiation in the retina of the zebrafish, Danio rerio. Journal of Comparative Neurology 371, 222–234.Google Scholar
Schmitt, E.A. & Dowling, J.E. (1999). Early retinal development in the zebrafish, Danio rerio: Light and electron microscopic analyses. Journal of Comparative Neurology 404, 515–536.Google Scholar
Shen, Y.C. & Raymond, P.A. (2004). Zebrafish cone-rod (crx) homeobox gene promotes retinogenesis. Developmental Biology 269, 237–251.Google Scholar
Smith, S.M. (1997). Alcohol-induced cell death in the embryo. Alcohol Health & Research World 21, 287–297.Google Scholar
Stenkamp, D.L., Frey, R.A., Mallory, D.E. & Shupe, E.E. (2002). Embryonic retinal gene expression in sonic-you mutant zebrafish. Developmental Dynamics 225, 344–350.Google Scholar
Stenkamp, D.L., Gregory, J.K. & Adler, R. (1993). Retinoid effects in purified cultures of chick embryo retina neurons and photoreceptors. Investigative Ophthalmology & Visual Science 34, 2425–2436.Google Scholar
Stenkamp, D.L., Hisatomi, O., Barthel, L.K., Tokunaga, F. & Raymond, P.A. (1996). Temporal expression of rod and cone opsins in embryonic goldfish retina predicts the spatial organization of the cone mosaic. Investigative Ophthalmology & Visual Science 37, 363–376.Google Scholar
Stratton, K.R., Howe, C. & Battaglia, F.C. (eds.). (1996). Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, DC: National Academy Press.
Stromland, K. (1985). Ocular abnormalities in the fetal alcohol syndrome. Acta Ophthalmologica Scandinavica 171, 1–50.Google Scholar
Stromland, K. (1987). Ocular involvement in the fetal alcohol syndrome. Survey of Ophthalmology 31, 277–284.Google Scholar
Stromland, K. & Pinazo-Duran, M.D. (2002). Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol and Alcoholism 37, 2–8.Google Scholar
Sulik, K.K. (2005). Genesis of alcohol-induced craniofacial dysmorphism. Experimental Biology and Medicine (Maywood) 230, 366–375.Google Scholar
Tenkova, T., Young, C., Dikranian, K., Labruyere, J. & Olney, J.W. (2003). Ethanol-induced apoptosis in the developing visual system during synaptogenesis. Investigative Ophthalmology & Visual Science 44, 2809–2817.Google Scholar
Westerfield, M. (2000). The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio). 4th ed. Eugene, OR: University of Oregon.
Yan, R.T. & Wang, S.Z. (1998). neuroD induces photoreceptor cell overproduction in vivo and de novo generation in vitro. Journal of Neurobiology 36, 485–496.Google Scholar
Zachman, R.D. & Grummer, M.A. (1998). The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome. Alcoholism: Clinical and Experimental Research 22, 1544–1556.Google Scholar