Angiopoietins in Diabetic Retinopathy: Current Understanding and Therapeutic Potential

Table 1

Overview of preclinical trials assessing the efficacy of Tie2 signalling for the treatment of DR.

Reference	Therapy	Therapeutic mechanism	Animal model	Inhibited angiogenesis?	Inhibited vasopermeability?	Comments
Joussen et al. [65]	IVT rAng1, Ad-Ang1	Upregulated Tie2 phosphorylation	STZ mouse	n/a	Yes	Also showed Ang1 protects against leukocyte-mediated EC damage
Nambu et al. [63]	Overexpression of Ang1 using transgenic model	Upregulated Tie2 phosphorylation	OIR mouse, laser-induced NV mouse	Yes	Yes
Nambu et al. [64]	Overexpression of Ang1 using transgenic model	Upregulated Tie2 phosphorylation	OIR mouse, laser-induced NV mouse	No	n/a	Prevented retinal detachment
Lee et al. [50]	IVT of rAng1	β5 integrin signalling	OIR mouse	Yes	Yes	Also shown to be effective in ROP
Shen et al. [68]	IVT of anti-Ang2 antibody	Upregulated Tie2 phosphorylation	OIR mouse	Yes	Yes
Cahoon et al. [66]	AAV2.COMP-Ang1	Upregulated Tie2 phosphorylation	InsIIAkita transgenic mouse	n/a	Yes	Also restored retinal neurophysiological responses

IVT = intravitreal injection; OIR = oxygen-induced retinopathy; STZ = streptozotocin; EC = endothelial cell; NV = neovascularisation; ROP = retinopathy of prematurity; InsIIAkita = mouse model of diabetes with mutated insulin II gene.