Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease

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Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease

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Title: Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease
Author: Goyal, Sunali; Chauhan, Sunil Kumar; Dana, Reza

Note: Order does not necessarily reflect citation order of authors.

Citation: Goyal, Sunali. 2012. “Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease.” Archives of Ophthalmology 130 (1) (January 1): 84. doi:10.1001/archophthalmol.2011.266.
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Abstract: Objective

To determine if blocking prolymphangiogenic factors like VEGF-C would suppress alloimmunity in dry eye disease (DED) using a murine model.

Methods

The effects of intraperitoneal injections of 400 μg of anti-VEGF-C antibody (treated group) and intraperitoneal normal saline (untreated group) were studied in murine dry eyes induced by exposing mice to high-flow desiccated air in the Controlled Environment Chamber (CEC). Growth of lymphatic vessels and infiltration of macrophages was evaluated by immunohistochemistry using CD31 (pan-endothelial marker), LYVE -1(lymphatic endothelial marker) and CD11b (monocytes/macrophages marker). Real time PCR was performed to quantify expression of different inflammatory cytokine transcripts in the conjunctiva and lymph nodes, and vascular endothelial growth factors and their receptors (VEGF-A, C, D/R2, R3) in the cornea.

Results

Blocking VEGF-C led to significant reduction in lymphatic caliber (P=0.025) and lymphatic area (P=0.006) in the corneas of DED mice. In addition to significantly decreasing (P=0.005) CD11b+ cells, anti-VEGF-C treatment significantly decreased transcript levels of VEGF-C (P=0.002), VEGF-D (P=0.014) and VEGFR-3 (P=0.023) in the corneas of treated group. Significant decrease in expression of inflammatory cytokines in the conjunctiva (IL1-α, P= 0.003; IL1-β, P= 0.025 and IL-6, P= 0.005) and lymph nodes (IFN-γ, P= 0.008; and IL-17, P= 0.003) was also seen with anti-VEGF-C treatment.

Conclusions

Treatment with anti-VEGF-C led to significant improvement in DED reflected by decrease in inflammation at the clinical, molecular, and cellular levels.
Published Version: 10.1001/archophthalmol.2011.266
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629840/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34387111
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