Excess caffeine exposure impairs eye development during chick embryogenesis

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.

Prenatal Caffeine Exposure and Child IQ at Age 5.5 Years: The EDEN Mother-Child Cohort

“…For linear regression analyses, β represents the change in IQ units. Third, we conducted sensitivity analyses to test the robustness of our findings by 1) adjusting for maternal pre-pregnancy caffeine intake, 2) adjusting for paternal caffeine intake during pregnancy (>2 vs. ≤2 cups/day), 3) defining maternal caffeine exposure during pregnancy as the number of coffee cups (≤1 cup/week; 2 cups/week to 1 cup/day; ≥2 cups/day), 4) defining tobacco smoking as a quantitative variable (mean number of cigarettes/day during pregnancy), 5) restricting the analysis to the nonsmoking subsample, 6) restricting the analysis to the non-heavily drinking sub-sample, 7) without adjusting for gestational age. Statistical analyses were performed using SAS 9.3 software (SAS Institute Inc, Cary, North Carolina).…”

“…Caffeine administered in large amounts has been associated with teratogenic effects (i.e. neural tube, eye, cleft, cardiovascular and angiogenesis malformations) (1)(2)(3)(4)(5). Prenatal caffeine exposure can also lead to postnatal cognitive and behavioral changes in grown-up rodent offspring.…”

Adenosine receptors and caffeine in retinopathy of prematurity

“…In particular, it should be noted that despite of lack of the general developmental effect on postnatal brain (specifically retinal vasculature) functions, there is lingering concerns on the possible specific effect of caffeine on embryonic development (Ma et al, 2014; Back et al, 2006) and possible postnatal development and maturation of cortical GABAergic neurons at the microstructural level by perinatal exposure to caffeine (Ardais et al, 2014; Silva et al, 2013). …”

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

“…As the eye is essentially a highly specialized extension of the brain, we decided to investigate the effect of salt-loading/treatment on eye development with special focus on the developing retina and lens. As a model for the experiment we chose the early chick embryo model because it corresponds to the first month of embryonic development in mammals with an eye structure that is big in size in proportion to the embryos body [26,27]. …”