Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-14T23:20:42.673Z Has data issue: false hasContentIssue false
  • English
  • Français

Early retinoic acid deprivation in developing zebrafish results in microphthalmia

Published online by Cambridge University Press:  27 September 2012

HONG-GAM T. LE ,
JOHN E. DOWLING  and
D. JOSHUA CAMERON
HONG-GAM T. LE
Affiliation:
Boston Foundation for Sight, Needham, Massachusetts Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts
JOHN E. DOWLING
Affiliation:
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts
D. JOSHUA CAMERON*
Affiliation:
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts College of Optometry, Western University of Health Sciences, Pomona, California
*
*Address correspondence and reprint requests to: Dr. D. Joshua Cameron, College of Optometry, Western University of Health Sciences, 701 E. Second Street, Pomona, CA 91766. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Vitamin A deficiency causes impaired vision and blindness in millions of children around the world. Previous studies in zebrafish have demonstrated that retinoic acid (RA), the acid form of vitamin A, plays a vital role in early eye development. The objective of this study was to describe the effects of early RA deficiency by treating zebrafish with diethylaminobenzaldehyde (DEAB), a potent inhibitor of the enzyme retinaldehyde dehydrogenase (RALDH) that converts retinal to RA. Zebrafish embryos were treated for 2 h beginning at 9 h postfertilization. Gross morphology and retinal development were examined at regular intervals for 5 days after treatment. The optokinetic reflex (OKR) test, visual background adaptation (VBA) test, and the electroretinogram (ERG) were performed to assess visual function and behavior. Early treatment of zebrafish embryos with 100 μM DEAB (9 h) resulted in reduced eye size, and this microphthalmia persisted through larval development. Retinal histology revealed that DEAB eyes had significant developmental abnormalities but had relatively normal retinal lamination by 5.5 days postfertilization. However, the fish showed neither an OKR nor a VBA response. Further, the retina did not respond to light as measured by the ERG. We conclude that early deficiency of RA during eye development causes microphthalmia as well as other visual defects, and that timing of the RA deficiency is critical to the developmental outcome.

Keywords

Vitamin AEye developmentVBAERGOKR
Type
Research Articles
Information
Visual Neuroscience , Volume 29 , Issue 4-5 , September 2012 , pp. 219 - 228
Copyright
Copyright © Cambridge University Press 2012

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

Adler, R. & Canto-Soler, M.V. (2007). Molecular mechanisms of optic vesicle development: Complexities, ambiguities and controversies. Developmental Biology 305, 1–13.CrossRefGoogle ScholarPubMed
Biehlmaier, O., Lampert, J.M., von Lintig, J. & Kohler, K. (2005). Photoreceptor morphology is severely affected in the beta, beta-carotene-15,15’-oxygenase (bcox) zebrafish morphant. The European Journal of Neuroscience 21, 59–68.CrossRefGoogle ScholarPubMed
Brockerhoff, S.E., Hurley, J.B., Janssen-Bienhold, U., Neuhauss, S.C., Driever, W. & Dowling, J.E. (1995). A behavioral screen for isolating zebrafish mutants with visual system defects. Proceedings of the National Academy of Sciences of the United States of America 92, 10545–10549.CrossRefGoogle ScholarPubMed
Brown, D. & Cox, A. (2009). Innovative uses of video analysis. The Physics Teacher 47, 145–150.CrossRefGoogle Scholar
Cameron, D.J. & Dowling, J.E. (2009). Temporal elimination of retinoic acid signaling alters eye development in zebrafish. In ARVO Meeting Abstracts April 11, 2009, Investigative Ophthalmology and Vision Science Vol. 50, pp. 4002. Ft. Lauderdale, FL.Google Scholar
Cameron, D.A., Gentile, K.L., Middleton, F.A. & Yurco, P. (2005). Gene expression profiles of intact and regenerating zebrafish retina. Molecular Vision 11, 775–791.Google ScholarPubMed
Cepko, C.L., Austin, C.P., Yang, X., Alexiades, M. & Ezzeddine, D. (1996). Cell fate determination in the vertebrate retina. Proceedings of the National Academy of Sciences of the United States of America 93, 589–595.CrossRefGoogle ScholarPubMed
Dowling, J.E. (2012). The Retina: An Approachable Part of the brain, Revised Edition. Cambridge, MA: Belknap press of Harvard University press.CrossRefGoogle Scholar
Duester, G. (2008 a). Keeping an eye on retinoic acid signaling during eye development. Chemico–Biological Interactions 178(1-3):178–181.CrossRefGoogle ScholarPubMed
Duester, G. (2008 b). Retinoic acid synthesis and signaling during early organogenesis. Cell 134, 921–931.CrossRefGoogle ScholarPubMed
Emran, F., Rihel, J., Adolph, A.R., Wong, K.Y., Kraves, S. & Dowling, J.E. (2007). OFF ganglion cells cannot drive the optokinetic reflex in zebrafish. Proceedings of the National Academy of Sciences of the United States of America 104, 19126–19131.CrossRefGoogle ScholarPubMed
Golzio, C., Martinovic-Bouriel, J., Thomas, S., Mougou-Zrelli, S., Grattagliano-Bessieres, B., Bonniere, M., Delahaye, S., Munnich, A., Encha-Razavi, F., Lyonnet, S., Vekemans, M., Attie-Bitach, T. & Etchevers, H.C. (2007). Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding protein receptor gene STRA6. American Journal of Human Genetics 80, 1179–1187.CrossRefGoogle ScholarPubMed
Higashijima, S., Okamoto, H., Ueno, N., Hotta, Y. & Eguchi, G. (1997). High-frequency generation of transgenic zebrafish which reliably express GFP in whole muscles or the whole body by using promoters of zebrafish origin. Developmental Biology 192, 289–299.CrossRefGoogle ScholarPubMed
Hogben, L. & Slome, D. (1931). The pigmentary effector system. VI. The dual character of endocrine co-ordination in amphibian color change. Proceedings of the Royal Society of London. Series B, Biological Sciences 108, 10–53.Google Scholar
Huang, Y.Y. & Neuhauss, S.C. (2008). The optokinetic response in zebrafish and its applications. Frontiers in Bioscience 13, 1899–1916.CrossRefGoogle ScholarPubMed
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 of the United States of America 93, 13298–13303.CrossRefGoogle ScholarPubMed
Hyatt, G.A., Schmitt, E.A., Marsh-Armstrong, N.R. & Dowling, J.E. (1992). Retinoic acid-induced duplication of the zebrafish retina. Proceedings of the National Academy of Sciences of the United States of America 89, 8293–8297.CrossRefGoogle ScholarPubMed
Isken, A., Golczak, M., Oberhauser, V., Hunzelmann, S., Driever, W., Imanishi, Y., Palczewski, K. & von Lintig, J. (2008). RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome. Cell Metabolism 7, 258–268.CrossRefGoogle Scholar
Khanna, H., Akimoto, M., Siffroi-Fernandez, S., Friedman, J.S., Hicks, D. & Swaroop, A. (2006). Retinoic acid regulates the expression of photoreceptor transcription factor NRL. The Journal of Biological Chemistry 281, 27327–27334.CrossRefGoogle ScholarPubMed
Kumar, S., Sandell, L.L., Trainor, P.A., Koentgen, F. & Duester, G. (2012). Alcohol and aldehyde dehydrogenases: Retinoid metabolic effects in mouse knockout models. Biochimica et Biophysica Acta 1821, 198–205.CrossRefGoogle ScholarPubMed
Leung, Y.F. & Dowling, J.E. (2005). Gene expression profiling of zebrafish embryonic retina. Zebrafish 2, 269–283.CrossRefGoogle ScholarPubMed
Leung, Y.F., Ma, P. & Dowling, J.E. (2007). Gene expression profiling of zebrafish embryonic retinal pigment epithelium in vivo. Investigative Ophthalmology and Visual Science 48, 881–890.CrossRefGoogle ScholarPubMed
Mahmoud, M.I., Potter, J.J., Colvin, O.M., Hilton, J. & Mezey, E. (1993). Effect of 4-(diethylamino)benzaldehyde on ethanol metabolism in mice. Alcoholism, Clinical and Experimental Research 17, 1223–1227.CrossRefGoogle ScholarPubMed
Mark, M., Ghyselinck, N.B. & Chambon, P. (2006). Function of retinoid nuclear receptors: Lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annual Review of Pharmacology and Toxicology 46, 451–480.CrossRefGoogle ScholarPubMed
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 of the United States of America 91, 7286–7290.CrossRefGoogle ScholarPubMed
Molotkov, A., Molotkova, N. & Duester, G. (2006). Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning. Development 133, 1901–1910.CrossRefGoogle ScholarPubMed
Muto, A., Orger, M.B., Wehman, A.M., Smear, M.C., Kay, J.N., Page-McCaw, P.S., Gahtan, E., Xiao, T., Nevin, L.M., Gosse, N.J., Staub, W., Finger-Baier, K. & Baier, H. (2005). Forward genetic analysis of visual behavior in zebrafish. PLoS Genetics 1, e66.CrossRefGoogle ScholarPubMed
Neuhauss, S.C., Biehlmaier, O., Seeliger, M.W., Das, T., Kohler, K., Harris, W.A. & Baier, H. (1999). Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish. The Journal of Neuroscience 19, 8603–8615.CrossRefGoogle ScholarPubMed
Pasutto, F., Sticht, H., Hammersen, G., Gillessen-Kaesbach, G., Fitzpatrick, D.R., Nurnberg, G., Brasch, F., Schirmer-Zimmermann, H., Tolmie, J.L., Chitayat, D., Houge, G., Fernandez-Martinez, L., Keating, S., Mortier, G., Hennekam, R.C., von der Wense, A., Slavotinek, A., Meinecke, P., Bitoun, P., Becker, C., Nurnberg, P., Reis, A. & Rauch, A. (2007). Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. American Journal of Human Genetics 80, 550–560.CrossRefGoogle Scholar
Perz-Edwards, A., Hardison, N.L. & Linney, E. (2001). Retinoic acid-mediated gene expression in transgenic reporter zebrafish. Developmental Biology 229, 89–101.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Roeser, T. & Baier, H. (2003). Visuomotor behaviors in larval zebrafish after GFP-guided laser ablation of the optic tectum. The Journal of Neuroscience 23, 3726–3734.CrossRefGoogle ScholarPubMed
Ross, S.A., McCaffery, P.J., Drager, U.C. & De Luca, L.M. (2000). Retinoids in embryonal development. Physiological Reviews 80, 1021–1054.CrossRefGoogle ScholarPubMed
Russo, J.E., Hauguitz, D. & Hilton, J. (1988). Inhibition of mouse cytosolic aldehyde dehydrogenase by 4-(diethylamino)benzaldehyde. Biochemical Pharmacology 37, 1639–1642.CrossRefGoogle ScholarPubMed
Sen, J., Harpavat, S., Peters, M.A. & Cepko, C.L. (2005). Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina. Development 132, 5147–5159.CrossRefGoogle ScholarPubMed
Sieving, P.A., Murayama, K. & Naarendorp, F. (1994). Push-pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave. Visual Neuroscience 11, 519–532.CrossRefGoogle ScholarPubMed
Stujenske, J.M., Dowling, J.E. & Emran, F. (2011). The bugeye mutant zebrafish exhibits visual deficits that arise with the onset of an enlarged eye phenotype. Investigative Ophthalmology and Visual Science 52, 4200–4207.CrossRefGoogle ScholarPubMed
von Frisch, K. (1911). Beiträge zur Physiologie der Pigmentzellen in der Fischhaut. Pflügers Archiv 138, 319–387.CrossRefGoogle Scholar
Wehman, A.M., Staub, W., Meyers, J.R., Raymond, P.A. & Baier, H. (2005). Genetic dissection of the zebrafish retinal stem-cell compartment. Developmental Biology 281, 53–65.CrossRefGoogle ScholarPubMed
Westerfield, M. (2000). The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio). Eugene, OR: University of Oregon Press.Google Scholar
White, T., Lu, T., Metlapally, R., Katowitz, J., Kherani, F., Wang, T.Y., Tran-Viet, K.N. & Young, T.L. (2008). Identification of STRA6 and SKI sequence variants in patients with anophthalmia/microphthalmia. Molecular Vision 14, 2458–2465.Google ScholarPubMed
Wilson, J.G., Roth, C.B. & Warkany, J. (1953). An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. The American Journal of Anatomy 92, 189–217.CrossRefGoogle ScholarPubMed
Zhang, C., Song, Y., Thompson, D.A., Madonna, M.A., Millhauser, G.L., Toro, S., Varga, Z., Westerfield, M., Gamse, J., Chen, W. & Cone, R.D. (2010). Pineal-specific agouti protein regulates teleost background adaptation. Proceedings of the National Academy of Sciences of the United States of America 107, 20164–20171.CrossRefGoogle ScholarPubMed