title: Early retinoic acid deprivation in developing zebrafish results in microphthalmia.
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.
authors.affiliation: Boston Foundation for Sight, Needham, Massachusetts, USA.
authors.forename: Hong-Gam T
authors.initials: HG
authors.lastname: Le
authors.forename: John E
authors.initials: JE
authors.lastname: Dowling
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Cameron
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004596:Electroretinography / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000473:pathology; D005123:Eye / Q000473:pathology; D007814:Larva; D008850:Microphthalmos / Q000209:etiology* / Q000503:physiopathology; D017120:Nystagmus, Optokinetic / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D012018:Reflex / Q000187:drug effects; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D015027:Zebrafish / Q000502:physiology*; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C007368:C.I. Solvent Yellow 56; D014212:Tretinoin; D010128:p-Aminoazobenzene