Ovarian hormone modulation of radiation-induced cataractogenesis: Dose-response studies

Robert M. Bigsby, Shailaja Valluri, Jennifer Lopez, Marc S. Mendonca, Andrea Caperell-Grant, Colleen des Rosiers, Joseph R. Dynlacht

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

PURPOSE. Epidemiologic data on the effects of female sex hormones in cataract formation are conflicting. With the use of a rat model of radiation-induced cataractogenesis, it was found that estrogen can either enhance or inhibit the progression of radiation cataracts, depending on when the hormone is administered. The present study was performed to further define radiation-hormone interactions during cataractogenesis. METHODS. In one experiment, rats were left ovary-intact or ovariectomized and were then irradiated with 2.5, 5, 10, or 15 Gy to one eye. In another experiment, ovariectomized rats were treated continuously with three different doses of estradiol through a slow-release capsule implanted subcutaneously, after which one eye was irradiated with 15 Gy. In all animals, cataract formation was followed by slit lamp examination at regular intervals. RESULTS. Latency to identification of cataracts decreased exponentially with increasing radiation dose. The presence of ovaries enhanced cataractogenesis when the eye was irradiated with 15 Gy, but there was no difference between ovary-intact and ovariectomized rats that were irradiated at lower doses. In ovariectomized rats irradiated with 15 Gy, estradiol increased the rate of progression of cataracts in a dose-dependent manner. The rate of cataract progression increased linearly with increasing estradiol dose; there was no sign of saturation at high estradiol doses, as would be expected from a receptormediated effect. CONCLUSIONS. Ovarian hormones enhance radiation-induced cataract formation; hormone supplementation experiments indicate that estrogen is responsible for this effect. The data suggest that the enhancing effect of estradiol is not mediated by its receptor, but this requires further study.

Original languageEnglish (US)
Pages (from-to)3304-3310
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number7
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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