Abstract | BACKGROUND: METHODS: We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also performed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling. RESULTS: Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those of ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect of exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling. CONCLUSIONS: Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. These studies suggest that FASD intervention strategies based upon augmentation of RA or Shh signaling may not prevent ethanol-induced microphthalmia.
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Authors | Bhavani Kashyap, Ruth A Frey, Deborah L Stenkamp |
Journal | Alcoholism, clinical and experimental research
(Alcohol Clin Exp Res)
Vol. 35
Issue 9
Pg. 1644-61
(Sep 2011)
ISSN: 1530-0277 [Electronic] England |
PMID | 21554333
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | 2011 by the Research Society on Alcoholism. |
Chemical References |
- Central Nervous System Depressants
- Hedgehog Proteins
- Vitamins
- Ethanol
- Tretinoin
- Acridine Orange
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Topics |
- Abnormalities, Drug-Induced
(metabolism, pathology)
- Acridine Orange
(metabolism)
- Animals
- Central Nervous System Depressants
(toxicity)
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian
(drug effects, metabolism)
- Ethanol
(toxicity)
- Female
- Hedgehog Proteins
(metabolism)
- Microphthalmos
(chemically induced, metabolism, pathology)
- Neurogenesis
- Retina
(embryology, metabolism, pathology)
- Signal Transduction
(drug effects)
- Transgenes
- Tretinoin
(metabolism, pharmacology, toxicity)
- Vitamins
(metabolism, pharmacology, toxicity)
- Zebrafish
(embryology, genetics, metabolism)
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