Excess caffeine exposure impairs eye development during chick embryogenesis

J Cell Mol Med. 2014 Jun;18(6):1134-43. doi: 10.1111/jcmm.12260. Epub 2014 Mar 17.

Abstract

Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1(+) cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression.

Keywords: Pax6; ROS; caffeine; chick embryo; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / toxicity*
  • Central Nervous System Stimulants / toxicity*
  • Chick Embryo
  • Embryonic Development / drug effects*
  • Eye Proteins / metabolism
  • Female
  • Homeodomain Proteins / metabolism
  • Immunoenzyme Techniques
  • Microphthalmos / chemically induced
  • Microphthalmos / embryology
  • Microphthalmos / pathology*
  • Orbital Diseases / chemically induced
  • Orbital Diseases / embryology
  • Orbital Diseases / pathology*
  • Organogenesis / drug effects*
  • Paired Box Transcription Factors / metabolism
  • Pregnancy
  • Retina / drug effects
  • Retina / embryology
  • Retina / pathology*

Substances

  • Central Nervous System Stimulants
  • Eye Proteins
  • Homeodomain Proteins
  • Paired Box Transcription Factors
  • Caffeine