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N. Kociok, S. Doehmen, A. M. Joussen; The Involvement of TNF- on the mRNA Expression of Pro-Inflammatory Cytokines and Angiogenic Factors in a Rat Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4969.
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© ARVO (1962-2015); The Authors (2016-present)
In diabetic retinopathy the dysregulation of pro and anti-inflammatory factors leads to activation of quiescent macrophages/microglia, leukostasis and subsequent vascular damage such as the increase of vascular permeability and capillary loss. Therefore we aimed to evaluate the involvement of the inflammatory cytokine TNF-α on the mRNA expression of other pro-inflammatory cytokines involved in the activation and directed migration of immune cells and of angiogenic factors in a rat model of early diabetic retinopathy.
Long Evans rats were made diabetic with streptozotocin (STZ). Confirmed diabetic animals (persistent hyperglycemia (> 250mg/100ml)) were treated subcutaneously with the p75 TNF-α receptor/Fc construct etanercept. The eyes were enucleated, RNA was isolated from the retinae and reverse transcribed. The mRNA expression of the cytokines in the retinae of diabetic rats and their controls was quantified by Real-Time RT-PCR.
The mRNA level of TNFα, MCP1/SCYA2, MIP1A/SCYA3, MIP1B/SCYA4, ICAM1, VEGF, and ANG1 was quantified in the retinae of STZ-induced diabetic rats and non-diabetic controls, treated or not-treated with the TNF receptor p75 fusion protein etanercept. In the retinae of diabetic rats elevated mRNA levels (1.5-fold to 6-fold) were measured of TNF-α, MCP1/SCYA2, MIP1A/SCYA3, ICAM1, VEGF, and ANG1, but not MIP1B/SCYA4 as compared to non-diabetic controls. Treatment with etarnecept reduced the mRNA expression in the diabetic rats to a level comparable to non-diabetic controls.
These data emphasize the role of TNF-α in diabetic retinopathy. Modulating the expression of pro and anti-inflammatory factors or the cognate receptors and downstream signaling steps that activate quiescent macrophages/microglia as well as inhibiting microglial secretion of angiogenic factors could be a potential therapeutic strategy for inhibiting diabetic retinopathy.
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