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Kristin J Al-Ghoul, Fareeha Mahmood; The Role of Cytokines in the Initiation of Diabetic Cataracts. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1209.
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To determine if specific cytokines are elevated in the eye during diabetic cataract formation in a streptozotocin (STZ)-induced diabetic rat model and to assess the direct effects of selected cytokines on lens fiber structure in whole-lens culture.
Wistar rats (125-150g, n=35) were injected with a single 75 mg/kg intravenous dose of STZ to induce diabetes. Untreated animals served as controls. Animals were euthanized at 1, 2, 3 and 4 weeks post-injection, blood glucose levels (BGL) were recorded and aqueous humor and vitreous humor were collected and frozen. Cytokine analysis was performed using a bead-based immunoassay for the following cytokines: IFN-γ, TNF, IL-1α, IL-2, IL-4, and IL-10, followed by flow-cytometric analysis. For whole lens culture, normal Wistar rat lenses (n=24 animals) were cultured with IL-1α or IL-4 or were untreated (controls). Following either 24 hours (OD) or 48 hours (OS) in culture, lenses were photographed, decapsulated and fixed for further structural analysis.
At 1 week post-injection, mean BGL of STZ-injected animals was 268 mg/dL compared to 102 mg/dL in controls, indicating successful diabetic induction. TNF, IL-1α, and IL-4 were increased during diabetes in either aqueous humor, vitreous humor or both compared to controls. TNF was increased in both aqueous and vitreous humors at approximately 4 weeks after diabetic induction. A marked increase in IL-1α levels was noted in aqueous humor as early as 1 week post-STZ injection. Specifically, aqueous humor samples showed a 5-fold increase by 1 week post-induction and an 8-fold increase by 4 weeks post-induction. An immediate increase in IL-4 was also detected at 1 week post-STZ injection in the vitreous humor; IL-4 concentration remained elevated throughout week 4. Lenses cultured with either IL-1α or IL-4 showed structural alterations such as sutural widening, foci of fiber end disruption and discrete superficial opacities, primarily on posterior surfaces, as early as 24 hours. Lenses cultured in media without cytokine remained transparent and lacked obvious structural alterations.
IL-1α and IL-4 increased immediately subsequent to diabetic induction, and treatment of normal lenses with these cytokines induced structural changes consistent with documented changes in diabetic cataracts. These findings suggest that IL-1α and IL-4 may be involved in the initiation of diabetic cataract formation.
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