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N. J. O'Connor, R. B. Silver; Ocular Mast Cells in Streptozotocin-Induced Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4899.
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The renin-angiotensin system (RAS) is believed to play a pathogenic role in diabetic retinopathy. We previously reported that mast cells express renin, the rate-limiting enzyme in the RAS cascade. Based on the fact that there is a resident population of mast cells in uvea and choroid and our observations that mast cells synthesize renin, the rate-limiting factor in ANG formation, we hypothesized that mast cells play a key role in the development of diabetic retinopathy.
To induce a type-I diabetic model, rats were injected with a single dose of streptozotocin (STZ) and were maintained with confirmed hyperglycemia for 2 months. Some animals were treated with the mast cell stabilizer, Na-cromolyn, topically administered to the eyes. Fluorescein retinal angiography was performed weekly over the 2-month time course to assess vascular leakage. At the 2-month end point eyes were dissected free of extra-orbital connective tissue, fixed and sectioned. Immunocytochemical staining for avidin, a mast cell marker and renin was performed and the sections analyzed for the number and anatomical distribution of mast cells.
Fluorescein angiography demonstrated increasing leakiness of the vasculature over time in the hyperglycemic state (STZ, n=3 rats vs con, n=3 rats). The leakiness was greatly diminished in eyes treated with the Na-cromolyn (n=3 rats), suggesting a role for mast cells in this process. Analyzing the number and spatial distribution of mast cells revealed differences between the diabetic and control eyes. At the 2-month time point the total number of avidin-positive mast cells increased in the ciliary body and anterior sclera of the diabetic rats (24 ±8 mast cells/section, STZ, n=3; vs 9 ±0.3 mast cells/section, con, n=3). This trend was also observed in the sections at the interface between choroid and RPE (23 ±9 mast cells/section, STZ vs 12 ±0.4 mast cells/section, con). In both STZ and control sections, the population of mast cells remained constant in the posterior sclera (11 ±2 mast cells/section, STZ vs 10 ±4 mast cells/section, con). Avidin-positive mast cells were renin-positive, which suggests a role for a local RAS in diabetic retinopathy.
Our results indicate that mast cells play a pivotal role in the vascular abnormalities associated with diabetic retinopathy. We propose that ocular mast cells may represent a novel therapeutic target in diabetic retinopathy.
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