High exogenous homocysteine modifies eye development in early chick embryos

BACKGROUND: Homocysteine is a nonessential aminoacid whose increase is related to the appearance of neural tube defects in humans. In chick embryos, high levels of homocysteine produce neural tube defects and alteration of neural crest cell migration. METHODS: In our study, 8 mul of L-homocysteine thiolactone (20 mumol) was added to chick embryos of Stages 3-8/10 (Hamburger and Hamilton, 1951), (12-38 hr of incubation). Three days later, 50 embryos, externally normal or carrying isolated spinal neural tube defects, were sectioned and stained by hematoxilin-eosin or anti-fibrillin-1 antibody. RESULTS: The eye showed alterations of the optic cup as microphthalmia, or lens dislocation. In both cases, the incidence of alterations diminished with the age of the homocysteine-increased embryos. Optic cup modifications are probably associated with central nervous system alterations, because most of the affected embryos exhibited isolated spinal neural tube defects and had altered neural crest cells. We have shown for the first time that high exogenous homocysteine during early development could produce a caudally-displaced lens axis before the zonule is formed. Fibrillin-1 is the main component of elastic microfibrils, and in the adult human it is seen as a protein particularly susceptible to homocysteine attack. CONCLUSIONS: Antibody staining against fibrillin-1 showed no evident morphological differences in distribution between experimental and control embryos in the lens, suggesting that fibrillin-1 was not the cause, and malformations may be attributed to other mechanisms. (C) 2003 Wiley-Liss, Inc.