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A Positive and Negative Bystander Effect Influences Cataract Outcome in the Irradiated Lens

^A Ophthalmology, ^B Environmental Health Sciences, ¹ Columbia University, New York, NY

Commercial Relationships: B.V. Worgul, None; N.J. Kleiman, None; J. David, None.

Support: DOE Grant DE–FG–02–02ER63440 and support from Research to Prevent Blindness Inc.

Abstract

Purpose:A growing body of data irrefutably demonstrates that exposing tissues to ionizing radiation affects not only the irradiated cells but also neighboring cells outside the field, the so–called bystander effect. Typically, the observed outcome is negative i.e., one where–in the unirradiated cells are adversely affected. Previously we confirmed early reports that partial shielding of an irradiated lens reduces cataract development in the exposed portion, a rare example of a positive bystander effect. We speculated that using appropriate dose regimes, with more extensive follow–up, a concomitant, negative effect might be discernible. This would be expressed by the irradiated portion having a cataractogenic influence on it’s non–exposed neighbors. An appreciation of this possibility is important not only to radiation risk assessment but also the understanding of lens biology and cataractogenesis. Methods: Brown Norway rats 28 ± 0.5 days old were used throughout. The animals, in groups of ten each included those with one eye partially shielded, one eye totally unshielded and one eye totally shielded. The eyes were exposed to 10 mGy and 50 mGy doses of 250 kVp X–rays. Contoured corneal shields protected half the lens during exposure in the partially shielded groups. The rats were slitlamp evaluated weekly for 14 months (35% lifespan) and the lenses assessed using Merriam/Focht radiation cataract scoring. Results: As was found previously, at significantly higher doses, protecting a section of the lens from exposure resulted in an ameliorating influence on cataractogenesis in the unprotected portion when compared to lenses irradiated in toto. There was a clear dose response in that changes appeared in the irradiated lenses earlier in the 50 mGy rats than in the 10 mGy exposed animals (Stage 1 CD₅₀’s were 10.25 ± 0.5 and 13.0 ± 0.75 months respectively). Onset time was not affected by shielding. Of moment, and heretofore never reported, was the finding that the unexposed portions of the partially shielded lenses manifested vacuoles and small discrete opacities with greater frequency than that of unirradiated or fully shielded control eyes. Conclusions:A positive bystander effect for cataract development occurs in the mammalian lens even at very low radiation doses. In concert with the protective effect is a negative bystander influence on the unirradiated lens regions. Because the overall cataractogenicity of a given radiation dose is reduced it appears that the positive bystander influence outweighs the converse negative bystander expression at the tissue level.

Keywords: cataract • pathobiology • pathology: experimental

© 2005, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.