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A. Lennikov, N. Kitaichi, S. Kase, S. Ishida, S. Ohno; Amelioration of UVB-Induced Photokeratitis in Mice by Heat Shock Protein 70 Upregulation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1570.
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Geranylgeranylacetone (GGA) induces heat shock protein (HSP) 70 and 90 in vivo and in vitro. Recent findings indicate that HSPs operate as intracellular chaperones against stress conditions inhibiting caspase-induced apoptosis. Acute ultraviolet (UV) exposure causes photokeratitis and induces various inflammatory changes in cornea. In the present study, we examined whether upregulation of HSP70 has therapeutic effects on UV-photokeratitis in mice.
GGA was emulsified with 0.5% gum arabic and distilled water containing 0.2% vitamin E.C57 BL/6 female mice were divided into 4 groups, An experimental groups of mice received the oral administration using feeding needles. GGA-treated (500 mg/kg/mouse) and UVB-exposed (400mJ/cm2) , GGA-untreated UVB-exposed (400mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naïve controls received vehicle alone. Eyeballs were collected 24 h after irradiation, and corneas were stained with H&E, TUNEL and anti-HSP70 antibody.
UVB irradiation caused disruption of the corneal basement membrane erosions and thinning of the corneal epithelium; however, the epithelium was well preserved after irradiation in GGA-treated mice. Fewer apoptotic cells (5.86 ± 6.89% ) were found in GGA-treated mice compared to GGA-untreated mice (19.69±16.27%) after UV exposure (p < 0.01). (Table 1). No changes from Naïve mice were observed in GGA-treated but not irradiated mice corneas. HSP70 expression was upregulated in GGA-treated corneas.
These findings demonstrate that oral administration of GGA ameliorated UV-induced corneal damage in mice. This association was attributable to the downregulation of apoptosis due to upregulation of HSP70 in vivo. The findings in the present study may help elucidate the potential efficacy of GGA in treating various conditions that cause ocular damage, such as UV exposure, corneal injury, heat stress, inflammation, infection, chemical factors, and other.
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