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Cysteine-rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy

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Journal of Cell Communication and Signaling Aims and scope

Abstract

The vasculature forms a highly branched network investing every organ of vertebrate organisms. The retinal circulation, in particular, is supported by a central retinal artery branching into superficial arteries, which dive into the retina to form a dense network of capillaries in the deeper retinal layers. The function of the retina is highly dependent on the integrity and proper functioning of its vascular network and numerous ocular diseases including diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity are caused by vascular abnormalities culminating in total and sometimes irreversible loss of vision. CCN1 and CCN2 are inducible extracellular matrix (ECM) proteins which play a major role in normal and aberrant formation of blood vessels as their expression is associated with developmental and pathological angiogenesis. Both CCN1 and CCN2 achieve disparate cell-type and context-dependent activities through modulation of the angiogenic and synthetic phenotype of vascular and mesenchymal cells respectively. At the molecular level, CCN1 and CCN2 may control capillary growth and vascular cell differentiation by altering the composition or function of the constitutive ECM proteins, potentiating or interfering with the activity of various ligands and/or their receptors, physically interfering with the ECM-cell surface interconnections, and/or reprogramming gene expression driving cells toward new phenotypes. As such, these proteins emerged as important prognostic markers and potential therapeutic targets in neovascular and fibrovascular diseases of the eye. The purpose of this review is to highlight our current knowledge and understanding of the most recent data linking CCN1 and CCN2 signaling to ocular neovascularization bolstering the potential value of targeting these proteins in a therapeutic context.

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Abbreviations

AGE:

Advanced glycation end-product

AMD:

Age-related macular degeneration

Ang:

Angiopoietin

CNV:

Choroidal neovascularization

ECM:

Extracellular matrix

GCL:

Ganglion cell layer

GFP:

Green fluorescent protein

IGF:

Insulin-like growth factor

IPL:

Inner plexiform layer

INL:

Inner nuclear layer

MMP:

Matrix metalloproteinase

OIR:

Oxygen-induced retinopathy

PDR:

Proliferative diabetic retinopathy

RPE:

Retinal pigment epithelium

ROP:

Retinopathy of Prematurity

ROS:

Reactive oxygen species

TGF:

Transforming growth factor

TNF:

Tumor necrosis growth factor

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was supported by grant from the National Eye Institute of the National Institutes of Health EY022091-01 and Research for the Prevention of Blindness Foundation.

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  1. Department of Cell Biology and Department of Ophthalmology, State University of New York (SUNY) Eye Institute Downstate Medical Center, 450 Clarkson Avenue, Box 5, Brooklyn, NY, 11203, USA

    Lulu Yan & Brahim Chaqour

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  1. Lulu Yan
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Correspondence to Brahim Chaqour.

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Yan, L., Chaqour, B. Cysteine-rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy. J. Cell Commun. Signal. 7, 253–263 (2013). https://doi.org/10.1007/s12079-013-0206-6

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