Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP105) Inhibition of radiation-induced cataractogenesis by estrogen.

Dynlacht, Joseph*,1, Valluri, Shailaja2, DesRosiers, Colleen1, Greer, Falon1, Caperell-Grant, Andrea3, Mendonca, Marc1, Lopez, Jennifer1, Bigsby, Robert3, 1 Radiation Oncology, Indianapolis, Indiana, United States of America2 Ophthalmology, Indianapolis, Indiana, United States of America3 Obstetrics and Gynecology, Indianapolis, Indiana, United States of America

ABSTRACT- We recently demonstrated that estrogen (17-beta-estradiol, E2) may increase the severity of and decrease the latent period for cataractogenesis in rats irradiated with 10-15 Gy of cobalt-60 gamma rays. However, in our previous study, E2 was administered to ovariectomized rats continuously during the time prior to, during, and after irradiation. In our current study, we sought to determine whether the timing of estrogen administration is important in the modulation of cataractogenesis. Silastic capsules containing 20 mg of E2 were implanted into ovariectomized female rats 1 week prior to, or immediately after irradiation of the right orbit with 15 Gy of cobalt-60 gamma rays using the Leksell Gamma Knife. The level of opacities in E2-treated ovariectomized animals was measured at 2-4 week intervals using a slit lamp, and data were compared to untreated, ovariectomized (control) rats. We found that administration of E2 prior to, during and after irradiation (continuous treatment) resulted in enhanced progression of cataracts compared to when the estrogen capsule was removed just after irradiation, but incidence of cataractous eyes was equivalent. When E2 treatment was initiated after irradiation there was no effect on the rate of cataract progression, but interestingly, a decrease in the cataract incidence was observed. We conclude that E2 may enhance or protect against radiation cataractogenesis, depending upon when it is administered relative to the time of irradiation.

Key words: cataracts, estrogen, Gamma Knife, eyes

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2005 RRS