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Sriharsha Nagaraj, Priyanka Chevour, Swaminathan Sethu, Santosh G K Gadde, Arkasubhra Ghosh; Soluble molecular mediators associated with Choroidal Neovascular Membranes (CNVM) in patient aqeous humor.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5804.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (ARMD) is a progressive disease of the eye resulting in vision loss. Advanced presentation of ARMD includes choroidal neovascularization membranes (CNVM) which is a destructive form of the disease. Molecular aetiopathogenesis underlying the progression of early-ARMD to CNVM is yet to be explored. VEGF- dependent and -independent angiogenic mechanisms in CNVM induction and progression require investigations. Our study panel included secreted cell adhesion molecules and immunomodulators in aqueous humor of CNVM patients.
All samples were collected after obtaining informed consent from patients, study was approved by IEC. Levels of various soluble proteins such as inflammatory cytokines, chemokines, secreted cell adhesion molecules and pro-angiogenic factors in aqueous humor and plasma were measured both in patients with CNVM (n=6) undergoing intravitreal anti-VEGF injections. Age-matched controls (n=19) included diabetic patients without ARMD or other retinal diseases undergoing ocular surgery as part of routine clinical care for treatment of visual impairment. Cytometric bead array was used for simultaneous detection and quantification of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-17F, IL-21, IL-23p40, IFN-α, IFN-γ, RANTES, TGF-β1, CXCL10(IP 10), CCL2 (MCP-1), CCL3(MIP-1α), CCL4(MIP-1β), CX3CL1(Fractalkine) VCAM1, ICAM1, E-Selectin, L-Selectin and VEGF. Statistical analysis was performed using GraphPad Prism Ver 6.
Significantly higher levels of pro-angiogenic factor, VEGF was observed in CNVM patients compared to controls as expected. Cell adhesion molecules, VCAM1 and L-selectin but not ICAM1 was significantly higher in CNVM patients (p<0.05). A significant increase in levels of a unique subset immunomodulatory chemokines/cytokines (Fractalkine, IP10, MIP1beta, MCP1, IL-2 and IL-8) in aqueous humor of CNVM patients was observed compared to controls.
The findings demonstrate a unique molecular profile which may contribute to progression of disease and influence outcome of anti-angiogenic therapy. Interestingly, the elevated Fractalkine, VCAM1 and L-Selectin may also positively influence pro-angiogenic mechanisms in a VEGF independent manner. Further studies would advance our understanding on CNVM pathogenesis and identify alternative and/or VEGF-independent treatment strategies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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