Photorefractive keratectomy procedures using ultraviolet (UV) excimer lasers are being considered as an alternative to surgery by knife. Of concern, however, is the fact that tissue ablation results in the exposure of adjacent structures to subablative doses of radiation, the long-term biological consequences of which are unknown: while avoiding gross histopathologic changes, UV excimer lasers might produce subtle alterations in DNA and gene expression with an eventual oncogenic outcome. We plan, therefore, to use cornea models (both cornea tissue from primate eyes irradiated in vivo and cultured human cornea cells irradiated in vitro) to examine the carcinogenic potential of laser radiation. In addition to measurements of DNA damage, Nucleic acid probe technology will be applied to detect changes in expression of genes (oncogenes and others) typically affected by a variety of carcinogens. Since radiation emitted by KrF excimer laser (248nm) is likely to be carcinogenic, studies will focus on tissues irradiated by this device in order to identify early molecular events of carcinogenesis in the cornea. Such molecular markers will serve in evaluating the safety of laser radiation at 193nm (ArF), currently considered for clinical application. Future studies will examine radiation at additional wavelengths and different intensities, in the pursuit of identifying radiation parameters with minimal long-term damage to cornea tissue surrounding an ablated site.
| Miller, A C; Gafner, J; Clark, E P et al. (1993) Differences in radiation-induced micronuclei yields of human cells: influence of ras gene expression and protein localization. Int J Radiat Biol 64:547-54 |
| Rimoldi, D; Flessate, D M; Samid, D (1992) Changes in gene expression by 193- and 248-nm excimer laser radiation in cultured human fibroblasts. Radiat Res 131:325-31 |
| Samid, D; Miller, A C; Rimoldi, D et al. (1991) Increased radiation resistance in transformed and nontransformed cells with elevated ras proto-oncogene expression. Radiat Res 126:244-50 |
| Rimoldi, D; Miller, A C; Freeman, S E et al. (1991) DNA damage in cultured human skin fibroblasts exposed to excimer laser radiation. J Invest Dermatol 96:898-902 |
