Excessive maternal caffeine exposure during pregnancy is cataractogenic for neonatal crystalline lenses in rats: a biomicroscopic and histopathologic study

Abstract

ABSTRACT.Purpose: To investigate histologically the influence of maternal caffeine exposure during pregnancy in vivo on crystalline lenses in neonatal rats. Methods: Experimentally naive, female Wistar-albino rats (200-220 g) were mated with adult male rats over 2 days for copulation. After confirming pregnancy with a vaginal smear method, 50 gravid rats (dams) were randomly divided into five groups (n ¼ 10 in each), consisting of one control and four experimental groups. Groups 1, 2 and 3 experimental dams were treated with intraperitoneal (i.p.) caffeine at doses of 25, 50 and 100 mg/kg/day, respectively, during pregnancy from gestational day 9 through to day 21. Group 4 dams were treated with caffeine in distilled water in a gavage at a dose of 50 mg/kg/day. Group 5 control dams were given i.p. saline solution daily for the same period. After normal delivery, the eyes were examined by slit-lamp biomicroscopy. The neonates were then killed by decapitation at postnatal days 1 or 30 and the eyes removed for histopathologic investigation of the lenses. Results: Group 1 and control eyes had normal anterior lens capsules with a single layer of anterior cuboidal epithelial cells, regularly oriented cortical and nuclear lens fibres, and a clear posterior lens capsule with no lining epithelial cells behind the equator. In the remaining groups, histopathologic findings suggesting cataractogenesis included eosinophilic degeneration, lens fibre cell swelling and liquefaction, central lens fibres with retained nuclei, and prominent epithelial cells lining the posterior lens capsule behind the equator. Moreover, some lenses in group 3 had immature cataract on slit-lamp biomicroscopic examination at postnatal day 30. Conclusion: Excessive maternal caffeine exposure during pregnancy had cataractogenic effects on developing crystalline lenses in newborn rat eyes, both macroscopically and histopathologically. If an appropriate dose of caffeine can be identified, caffeine-induced cataract formation may be used as a new experimental cataract model in animal studies.

Ultrastructural changes in the developing chicken cornea following caffeine administration.

“…The occurrence of cataract on slit-lamp biomicroscopic examination at postnatal day 30 was observed in the experimental group, which was treated with caffeine at a dose of 100 mg/kg/day [23]. Lens formation can be impaired by a toxic injury induced by caffeine consumption in pregnancy and resulting in the development of cataract that is associated with abnormalities in the cells of the developing lens.…”

“…In an experimental study performed by Evereklioglu et al [23,24], the effect of caffeine administered to pregnant rats during the period of organogenesis in rats (from day 9 through day 20 of gestation) on the formation of neonatal cornea and lens in their offspring was investigated. There were no macroscopic corneal abnormalities in the newborn litters of experimental or control animals.…”

Evaluation of the reproductive and developmental risks of caffeine

“…Evereklioghi et al (2003, 2004) administered caffeine i.p. to Wistar rats on post conception days 9 to 21.…”

“…Two publications (Evereklioglu et al, 2003, 2004) reported results from the same set of rats. The Evereklioglu et al (2003) study was designed to identify whether histopathology could reveal changes in the neonatal rat cornea resulting from caffeine exposure during pregnancy.…”

The effects of prenatal exposure to methylxanthines

“…Evereklioglu et al (2004) conducted a histopathologic investigation on lenses isolated from newborn rats whose dam was given caffeine during pregnancy. They found cataractogenic changes pronounced in a dose-dependent manner.…”