Effects of ethanol on photoreceptors and visual function in developing zebrafish.
OBJECTIVE
Children born to mothers who have consumed alcohol during pregnancy have an array of retinal abnormalities and visual dysfunctions. In the past, rodent systems have been used to study the teratogenic effects of ethanol on vertebrate embryonic development. The exact developmental windows in which ethanol causes specific developmental defects have been difficult to determine because rodents and other mammals develop in utero. In this study, we characterized how ethanol affects the function and development of the visual system in an ex utero embryonic system, the zebrafish.


METHODS
Zebrafish embryos were raised in fish water containing various concentrations of ethanol from 2 to 5 days after fertilization. The effects of ethanol on retinal morphology were assessed by histologic and immunohistochemical analyses and those on retinal function were analyzed by optokinetic response (OKR) and electroretinography (ERG).


RESULTS
Zebrafish embryos exposed to moderate and high levels of ethanol during early embryonic development had morphological abnormalities of the eye characterized by hypoplasia of the optic nerve and inhibition of photoreceptor outer segment growth. Ethanol treatment also caused an increased visual threshold as measured by the OKR. Analysis with the ERG indicated that there was a severe reduction of both the a- and b-waves, suggesting that ethanol affects the function of the photoreceptors. Indeed, low levels of ethanol that did not cause obvious morphologic changes in either the body or retina did affect both the OKR visual threshold and the a- and b-wave amplitudes.


CONCLUSIONS
Ethanol affects photoreceptor function at low concentrations that do not disturb retinal morphology. Higher levels of ethanol inhibit photoreceptor development and cause hypoplasia of the optic nerve.
Matsui
Jonathan I
JI
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. jmatsui@fas.harvard.edu
Egana
Ana L
AL
Sponholtz
Todd R
TR
Adolph
Alan R
AR
Dowling
John E
JE
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004596:Electroretinography; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D017120:Nystagmus, Optokinetic / Q000187:drug effects / Q000502:physiology; D009900:Optic Nerve / Q000002:abnormalities; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000502:physiology; D012160:Retina / Q000196:embryology / Q000503:physiopathology; D012684:Sensory Thresholds; D014792:Visual Acuity / Q000187:drug effects*; D015027:Zebrafish / Q000196:embryology*
D002492:Central Nervous System Depressants; D000431:Ethanol