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B.V. Worgul, N.J. Kleiman, J. David; Studies on a Protective Bystander Effect in the Lens . Invest. Ophthalmol. Vis. Sci. 2004;45(13):381.
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Purpose: Some years ago several lens researchers described a phenomenon wherein partial shielding of an irradiated lens reduced the severity of the opacity which developed in the exposed portion. After the initial reports little work was done to elucidate the nuances of this now recognized protective, or positive, "bystander effect". For a variety of tissues and cell systems the role of bystanders in pathogenic expression has become the focus of intense investigative attention. Our effort is directed at fully detailing the bystander effect on lens opacification as well as the cellular changes attending cataractogenesis. Ultimately the goal is to identify the mechanism whereby the bystanders confer this protection. Methods: Lenses of Brown Norway rats 28 +/– 0.5 days old were irradiated either in situ or in organ culture. A variety of shields were fabricated to allow selected lens areas to be protected. The eyes, or isolated lenses, were exposed to 300 kVp X–rays at doses from 10 mGy to 10 Gy. For cataract studies the rats were followed for 1 year (∼30% lifespan) while lenses irradiated in vivo and in vitro were assessed by quantitative cytopathology at post exposure intervals ranging from hours to weeks. Results: At all doses examined, opacification in the exposed lens segment began approximately at the same time as in the totally unshielded controls but in all cases the severity of the opacity in the affected region at any given time was measurably less than had the entire lens been exposed. Cellular changes known to quantitatively presage the eventual cataract were all reduced in the exposed quadrants in comparison to the same areas in whole lens exposures. The endpoints included mitotic aberrations, hyperploidy, micronucleation, rosette formation and failed differentiation. The ameliorative effect of an unexposed region was also very evident in cell killing and cell depletion in the irradiated zone. Of note it was found that interphase death due to radiation does not involve typical apoptotic pathways. Conclusions: A protective bystander effect for cataract development occurs in the mammalian lens. Although onset is not affected, progression of radiogenic opacification is reduced by the presence of non–irradiated lens constituents. Cataract–related cytopathological expression is also diminished. Unlike other systems, this positive bystander effect does not appear to be associated with a selective removal of damaged cells by cell death since cell death is also reduced. A model dependent on the extensive gap–junction network characteristic of lens cytoarchitecture is currently being investigated for a role in the observed protection.
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