NEUROPROTECTIVE EFFECT ON UV-C EXPOSED HUMAN RETINAL CELLS.
A.W. von Deutsch1,2, D.A.
von Deutsch2,3,4, I.K.
Ellerson5 , K. Dutt6,
T.C. Chu3, and S. Houston2.
1Collins Hill High
School, Lawrenceville, GA.; 2Space
Medicine and Life Sciences Research Center,
Pharmacology & Toxicology, and the
Center, 5Department of
Biochemistry, Immunology, and Microbiology,
6Department of Pathology,
Morehouse School of Medicine, Atlanta, GA 30310.
astronauts are continuously exposed to low levels of radiation and experience
varying degrees of ischemia and reperfusion-related oxidative damage.
Furthermore, oxidative stress can also arise from ionizing and ultraviolet
radiation (UV). The latter provides a relatively safe approach for studying
the effects of radiation-induced free radical-mediated cellular damage. The
purpose of this study was two fold. First, to establish the extent
of UV-induced damaged in human retinal cells and second, to find whether
damage could be attenuated by treatment with 10-7 M
clenbuterol, a ß2-adrenergic
agonist. Methods. Human fetal retinal cells were cultured in
6-well trays with half of the wells receiving treatment and the other vehicle
(PBS). Trays were exposed to UV-C for varying lengths of time (0, 15, 30, 60,
and 90 minutes). At 24 hours post-exposure, the trays were pulled and cell
vitality was checked by dye exclusion assay. Subsequent experiments used a
fixed exposure time of 90 minutes to UV-C to determine the effects of the ß2-adrenoceptor
antagonist ICI-118551 (10-6 M)
and the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO, 10-5 M)
on clenbuterol's protective effects. Results. Treatment with 10-7 M
clenbuterol significantly reduced the rate of cell death due to UV-C exposure
at all exposure times. Furthermore, the ß2-adrenoceptor
antagonist ICI-118551 significantly attenuated clenbuterol's protective effect
while DFMO completely blocked it. Conclusions: This study
suggests that the neuroprotective effect of clenbuterol is mediated through
(This work was supported,
in part, by NASA Grant NCC9-112 and NIH Grants RCRII 2P20, RR11104-09, and