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Imran Bhutto, Joseph Yates, Mary Johnson, Carol Merges, Barbara Hansen, Gerard Lutty; Expression of Inflammatory Mediators in Eyes of Spontaneously Type-2 Diabetic Monkeys. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2686. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is a chronic complication of diabetes, characterized by degeneration of neurons and glial activation accompanied by diffuse vascular abnormalities. However, the mechanisms of vascular pathology in DR are not yet fully understood but increasing evidence indicates that inflammation plays a key role in the pathogenesis of DR. The increased expression of adhesion molecules and inflammatory cytokines, as well as microglial activation in the retina or vitreous, all suggest that local inflammation may represent the central pathway leading to DR. In the present study, we examined the expression and localization of inflammatory mediators in spontaneously diabetic and nondiabetic rhesus monkey eyes.
Eyes from 9 spontaneously type-2 diabetic and 8 normotensive non-diabetic rhesus monkeys were evaluated. Alkaline phosphatase immunohistochemistry was performed using monoclonal and/or polyclonal antibodies against inflammatory mediators on cryopreserved sections from disk/macular blocks. Pigment in retinal pigment epithelium (RPE) and choroidal melanocytes was bleached. Three independent masked observers scored the reaction product (scored from 0-8). Mean scores from the diabetic and the eyes with non-diabetes were analyzed using 1-way analysis of variance and unpaired Student t-test.
The expression of ICAM-1, TNF-α, VEGF, CRP, and MCP-1 was significantly higher in retinal and choroidal blood vessels in diabetic monkeys and were associated with severity of diabetes. ICAM-1 was significantly higher in neural retina (p≤0.02) of diabetic eyes and ICAM-1, TNF-α, and VEGF were significantly higher in RPE of diabetic than nondiabetic monkey eyes. IL-6 was more intense and significantly higher in Bruchs membrane/choriocapillaris complex (BrM/CC) (p≤0.045) including intercapillary septa (ICS) (p≤0.009) in diabetic monkey choroids. IP-10 was more prominent in melanocytes in diabetic choroids (p≤0.03). The number of MHCII positive cells was significantly higher in diabetic monkey choroids.
These immunohistochemical findings showed an increased expression and relative levels of inflammatory mediators in diabetic monkey eyes. These data support the role of inflammation in the pathogenesis of type 2 diabetes. Targeting a combination of proinflammatory mediators, simultaneously, may be an effective strategy for the treatment of diabetic retinopathy.
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