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COMP‐Ang1 preserves vasculature and prevents vision loss in diabetic retinopathy
Author(s) -
Cahoon Judd Michael,
Olson Paul Robert,
Zhang Xiao Hui,
Flood Maggie Marie,
Archer Bonnie,
Ambati Balamurali Krishna
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.8
Subject(s) - pericyte , diabetic retinopathy , medicine , angiopoietin , retinal , ischemia , vascular permeability , population , diabetes mellitus , inflammation , ophthalmology , vascular endothelial growth factor , endocrinology , endothelial stem cell , biology , vegf receptors , biochemistry , environmental health , in vitro
Diabetic retinopathy (DR) is the most common cause of blindness in the working‐age population. Vascular dysfunction is a hallmark of DR. Prolonged hyperglycemia results in loss of pericytes, the support cells that surround the capillary. An important pericyte derived trophic factor is angiopoietin‐1 (Ang‐1), which binds to the endothelial Tie2 receptor. Loss of pericytes and decreased Ang1 has been described as an early event in diabetic retinopathy. Here we show that vascular normalization with cartilage oligo matrix protein angiopoietin 1 (COMP‐Ang1) prevents endothelial dropout and the critical sequelae of ischemia and hyperpermeability in a mouse model of DR. COMP‐Ang1 increased VE‐cadherin expression and decreased VEGF‐A expression in the diabetic mouse retina. COMP‐Ang1 preserved vascular network area comparable to non‐diabetic control levels, despite persistent pericyte dropout. Additionally, COMP‐Ang1 decreased retinal inflammation, as noted by decreased leukocyte adhesion and infiltration. Furthermore, AAV2.COMP‐Ang1 therapy prevented retinal thinning and ganglion cell layer dropout. Most importantly, diabetic mice treated with COMP‐Ang1 retained near‐normal visual acuity and electroretinographic response. COMP‐Ang1 may be useful in promoting vascular normalization by reducing ischemia and hyperpermeability in diabetic retinopathy.