Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

Table 1

Biological actions of endogenous inhibitors of angiogenesis.

Endogenous inhibitor	Functions
PEDF, serine protease	Increases survival of neuronal cell, preserves the integrity of neuronal cells; protects neuronal cells from apoptosis,; decreases proliferating endothelial cells,; decreases expression of inflammatory molecules like TNF and iNOS.
Angiostatin, cleaved product of plasminogen containing the kringle domains 1–4	Increases apoptosis of proliferating vascular endothelial cells,; decreases proliferation and migration of endothelial cells,; decreases recruitment and adhesion of inflammatory cells to the endothelium, and decreases transmigration of inflammatory cells.
Endostatin, fragment of collagen XVIII	Increases apoptosis and decreases migration of cells involved in active neovascularisation, blocks the binding of VEGF to KDR/Flk-1, and decreases spontaneous release of VEGF from endothelial cell culture,; structurally supports role of the Bruch’s membrane.
TIMP3, inhibitor of matrix metalloproteinase	Increases apoptosis and decreases migration of cells involved in active neovascularisation, blocks the binding of VEGF to KDR/Flk-1,; structurally supports role of the Bruch’s membrane.
Vasostatin, a derivative from the NH2 terminal domain of a calcium binding protein calreticulin	Decreases proliferation of endothelial cells,; decreases adhesion of leukocytes to endothelium,; decreases expression of vascular destabilising factor angiopoietin 2.
Plasminogen kringle 5, cleaved product of plasminogen containing the kringle domain 5	Increases proliferation and decreases migration of endothelial cells,; increases apoptosis of endothelial cells,; increases infiltration of inflammatory cells.
Thrombospondin-1, glycoprotein	Decreases apoptosis of endothelial cells,; decreases expression of inflammatory molecules.