Effect of Geranylgeranylacetone on Ultraviolet Radiation Type B-Induced Cataract in Heat-Shock Transcription Factor 1 Heterozygous Mouse.

Purpose: We investigated whether heat-shock transcription factor 1 (HSF1) was involved in ultraviolet radiation type B (UVR-B)-induced lens opacity (cataract) using HSF1 heterozygous mice. We also examined the effects of geranylgeranylacetone (GGA), an inducer of heat-shock proteins via activation of HSF, on the UVR-B-induced cataract.

Material And Methods: Male HSF1 and WT mice were unilaterally exposed to UVR-B (total: 1200mJ) at 16 weeks of age. At 48 h after the last UVR-B irradiation, the lens was isolated and the induction of the cataract was quantified as the cataract area ratio (opacity area/anterior capsule). GGA was orally administered at a dosage of 500 mg/kg once a day for two days before the first UVR-B exposure until the end of the experiment (21days in total).

Results: The HSF1 expression was more greatly decreased in the lens from HSF1 mice than in that from WT mice (p < 0.01). UVR-B exposure could mainly induce cataracts in the anterior capsule in both HSF1 and WT mice, while the opacity of the lens was markedly enhanced in HSF mice compared to that in WT mice(p (0.01). GGA treatment could prevent the induction of lens opacity by UVR-B exposure in both WT and HSF1 mice as compared with the non-administration group (p < 0.01). No obvious alteration by the UVR-B radiation was seen in lens protein levels of αA-crystallin, αB-crystallin, or γ-crystallin with or without GGA administration among all groups of mice. In contrast to the crystallins, the lens protein level of HSP25 was decreased by UVR-B exposure in both HSF1 and WT mice, and was significantly recovered in WT mice by the GGA treatment (p < 0.01). The induction of HSP25 was suppressed in HSF1 mice compared with that in WT mice.

Conclusions: These data suggest that HSF1 plays an important role in the occurrence of UVR-B-induced cataracts, possibly via regulation of HSPs such as HSP25.