Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: diabetes • diabetic retinopathy