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F. Chaabo, S. Nakao, N. Lara-Castillo, S. Zandi, K. Noda, A. Hafezi-Moghadam; Time-Dependent Inhibition of Inflammatory Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1954.
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Ocular Inflammation, aging, and diabetic retinopathy (DR) can cause angiogenesis and significant vision loss. Steroids are the mainstay of current anti-inflammatory and angiostatic treatment in the eye, in spite of various side effects. Timing of the treatment may be critical for successful outcome, and should be based on experimental evidence. This work elucidates the optimal start point for steroid therapy in inflammatory angiogenesis.
Angiogenesis was induced using the corneal micropocket assay. Male Balb/c mice were anesthetized, and hydron pellets (0.3µl), containing mouse IL-1beta (30ng), were implanted into the corneas. 2, 4 and 6 days after pellet implantation, intraperitoneal treatment of dexamethasone (5mg/kg), a synthetic corticosteroid analogue, was started. Photographs were obtained 2, 4, 6, 10, and 14 days after IL-1beta implantation. The area of angiogenesis, the number of vessels, and the portion of vascular tips were examined on each day.
Dexamethasone treatment starting on day 2 after IL-1beta implantation significantly reduced angiogenesis, compared to the untreated control. In this group complete regression of the angiogenic vessels was observed by day 10 and 14. When treatment started on day 4, corneal vascular plexus (vascular area, number of vessels, and portion of vascular tips) was significantly less compared with untreated controls on day 14 after pellet implantation (vascular area, 0.48±0.1 vs 1.17±0.18mm2, n=4-6, P=0.004; number of vessels, 4.0±1.3 vs 11.3±1.6, n=4-6, P=0.007; portion of vascular tips, 0.94±0.1 vs 1.5±0.1, n=5-8, P=0.002, respectively). When the treatment started after day 6, dexamethasone did not change IL-1beta-induced corneal angiogenesis, compared with untreated controls until day 14 (vascular area,1.0±0.1 mm2, n=4, P=0.5; number of vessels, 10.3±1.5, n=4, P=0.7; portion of vascular tips, 1.5±0.2, n=4, P=0.9).
We demonstrate that the time point of the antiangiogenic treatment is critical for effective inhihibition of corneal angiogenesis. Complete regression of inflammatory angiogenesis is achieved with early treatment. However, after a critical time point angiogenesis may be irreversible.
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