Abstract
Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP)70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice. C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and protein kinase B (Akt) expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01). Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01). Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0.05). ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation.
Highlights
Ultraviolet (UV) irradiation is one of the several environmental hazards that may cause inflammatory reactions in ocular tissues
UVB exposure affects all tissues of the cornea [2] and causes apoptosis in corneal cells by direct cell membrane damage, deoxyribonucleic acid (DNA) damage, reactive oxygen species (ROS) induction, as well as a result of an inflammatory reaction
We previously demonstrated that GGA administration had protective effects against ocular inflammatory disorders such as ischemia-induced retinal injury and experimental autoimmune uveoretinitis (EAU) in murine models [6,7]
Summary
Ultraviolet (UV) irradiation is one of the several environmental hazards that may cause inflammatory reactions in ocular tissues. UVB exposure affects all tissues of the cornea [2] and causes apoptosis in corneal cells by direct cell membrane damage, deoxyribonucleic acid (DNA) damage, reactive oxygen species (ROS) induction, as well as a result of an inflammatory reaction. GGA induces heat shock protein (HSP) expression, as reported previously [4]. We previously demonstrated that GGA administration had protective effects against ocular inflammatory disorders such as ischemia-induced retinal injury and experimental autoimmune uveoretinitis (EAU) in murine models [6,7]. Recent reports indicated that HSP70 activated protein kinase B (Akt) phosphorylation, inhibiting dephosphorylation and further activation of cell death pathways in the photorecepter cells of the eye [13] and ameliorated H2O2-induced apoptosis of corneal epithelial cells by suppressing caspase-3 and caspase-9 in vitro [14]. We investigated whether oral administrations of GGA induced a protective effect against UV-induced corneal damage in mice
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