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Sriharsha Nagaraj, Bharat Thyagarajan, Santosh GopiKrishna, Naresh Kumar Yadav, Rohit Shetty, Arkasubhra Ghosh; Molecular analysis of ocular inflammatory pathways driving diabetic retinopathy patients undergoing anti-VEGF therapy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4680.
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© ARVO (1962-2015); The Authors (2016-present)
This study aims to evaluate the role of inflammatory response to neovascularization in the pathogenesis of diabetic retinopathy. While the role of anti-VEGF treatment is well known in patients with retinopathy, the role of inflammation during the response to therapy is poorly understood. Hence, we aim to discover novel ocular inflammatory biomarkers that can be used to identify individuals at increased risk for developing diabetic retinopathy and possible response to anti-VEGF treatment who may benefit from targeted prevention strategies.
All samples were collected after informed written consent and with approval of the Institutional Ethics Committee. Aqueous humor was collected from patients undergoing intravitreal injections or ocular surgery as part of routine clinical care for treatment of visual impairment. The experimental cohort consisted of cataract patients without DR (n=3), NPDR patients with early macular edema (E-ME) undergoing their first intravitreal anti-VEGF injection (n=3), PDR patients with persistent macular edema (P-ME), who have underwent at least 3 intravitreal anti-VEGF injections (n=3), PDR patients with severe edema and vitreal hemorrhage (VH) who have undergone at least 3 prior intra-vitreal injections (n=4). The levels of various inflammatory biomarkers, regulatory cytokines and pro-angiogenic factors were measured using a multiplexed CBA (Cytometric Bead Array) assay on a BD FACS Caliber flow cytometer.
The data shows VEGF levels were higher in the retinopathy patients compared to controls. However, VEGF levels were lower in patients with repeated anti-VEGF injections compared to the E-ME group. Additionally, we observed upregulation of pro-angiogenic factors [CD54 (ICAM1)] and pro-inflammatory markers [IL6, IL8, MCP1 and IP10] and regulatory cytokines in P-ME and VH groups and a corresponding downregulation of anti-inflammatory cytokine such as IL-12p70 in the P-ME and VH groups.
The data demonstrate a unique interplay between the inflammatory cytokines IL6, IL8, MCP1 and IP10 with ICAM1 and regulatory cytokine IL12p70. Results also suggest that inflammatory cytokine levels are higher in persistent macular edema and vitreal haemorrhage patients despite reduction in VEGF levels. Further confirmation of the data and investigation of underlying molecular pathways may help clinical management of diabetic retinopathy.
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