Regulation of Blood Vessel Versus Lymphatic Vessel Growth in the Cornea

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2008 Nov 26

PMID 19029028

Citations 22

Authors

Eui-Sang Chung

Daniel R Saban

Sunil K Chauhan

Reza Dana

Affiliations

Soon will be listed here.

Abstract

Purpose: In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea.

Methods: Micropellets loaded with high-dose (80 ng) or low-dose (12.5 ng) basic fibroblast growth factor (bFGF) were placed in BALB/c corneas. Angiogenic responses were analyzed by immunohistochemistry to quantify blood neovessels (BVs) and lymphatic neovessels (LVs) to 3 weeks after implantation. Areas covered by BV and LV were calculated and expressed as a percentage of the total corneal area (percentage BV and percentage LV). Hemangiogenesis (HA) and lymphangiogenesis (LA) were also assessed after antibody blockade of VEGFR-2 or VEGFR-3

Results: Although high-dose bFGF stimulation induced a more potent angiogenic response, the relative LV (RLV=percentage LV/percentage BV x 100) was nearly identical with high- and low-doses of bFGF. Delayed LA responses induced 3 weeks after implantation of high-dose bFGF resulted in a lymphatic vessel-dominant phenotype. Interestingly, the blockade of VEGFR-2 significantly suppressed BV and LV. However, the blockade of VEGFR-3 inhibited only LV (P=0.0002) without concurrent inhibition of BV (P=0.79), thereby resulting in a blood vessel-dominant phenotype

Conclusions: An HA-dominant corneal phenotype can be obtained in BALB/c mice 2 weeks after implantation of an 80-ng bFGF micropellet with VEGFR-3 blockade. Alternatively, an LA-dominant corneal phenotype can be obtained 3 weeks after implantation of an 80-ng bFGF micropellet without supplementary modulating agents. These models will be useful in evaluating the differential contribution of BV and LV to a variety of corneal abnormalities, including transplant rejection, wound healing and microbial keratitis.

Citing Articles

Interaction Between Blood Vasculatures and Lymphatic Vasculatures During Inflammation.

Wang S, Zhu X, Wu X, Zhang W, Ding Y, Jin S J Inflamm Res. 2023; 16:3271-3281.

PMID: 37560514 PMC: 10408656. DOI: 10.2147/JIR.S414891.

Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.

Patnam M, Dommaraju S, Masood F, Herbst P, Chang J, Hu W Cells. 2023; 12(2).

PMID: 36672254 PMC: 9856498. DOI: 10.3390/cells12020319.

Corneal Lymphangiogenesis: Current Pathophysiological Understandings and Its Functional Role in Ocular Surface Disease.

Lee H, Lee S, Lee D Int J Mol Sci. 2021; 22(21).

PMID: 34769057 PMC: 8583961. DOI: 10.3390/ijms222111628.

Spatial Distribution of Mast Cells Regulates Asymmetrical Angiogenesis at the Ocular Surface.

Cho W, Mittal S, Elbasiony E, Chauhan S Am J Pathol. 2021; 191(6):1108-1117.

PMID: 33705754 PMC: 8176138. DOI: 10.1016/j.ajpath.2021.02.016.

Activation of ocular surface mast cells promotes corneal neovascularization.

Cho W, Mittal S, Elbasiony E, Chauhan S Ocul Surf. 2020; 18(4):857-864.

PMID: 32916251 PMC: 7686271. DOI: 10.1016/j.jtos.2020.09.002.

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