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The Role of Angiopoietins in Neovascular Diabetes-Related Retinal Diseases
Juan David Collazos-Alemán1, Sofía Gnecco-González1, Beatriz Jaramillo-Zarama1
1School of Medicine, Universidad de los Andes, Carrera 7 No 116-05, Of 413, Bogotá, Colombia.
Abstract:
Diabetic retinopathy is a devastating and frequent complication of poorly controlled diabetes, whose pathogenesis is still only partially understood. Advances in basic research over the last two decades have led to the discovery of angiopoietins, proteins that strongly influence the growth and integrity of blood vessels in many vascular beds, with particular importance in the retina. Angiopoietin 1 (Ang1), produced mostly by pericytes and platelets, and angiopoietin 2 (Ang2), produced mainly by endothelial cells, bind to the same receptor (Tie2), but exert opposing effects on target cells. Ang1 maintains the stability of the mature vasculature, while Ang2 promotes vessel wall destabilization and disruption of the connections between endothelial cells and pericytes. Human retinal endothelial cells exposed to Ang2 show reduced membrane expression of the adhesion molecule VE-cadherin, and patients with proliferative diabetic retinopathy or diabetic macular edema have markedly increased vitreal concentrations of Ang2. Faricimab, a bi-specific antibody simultaneously directed against Ang2 and VEGF, has shown promising results in clinical trials among patients with diabetic retinopathy, and other agents targeting the angiopoietin system are currently in development.
Insights
Diabetic retinopathy involves blood vessel complications. Targeting angiopoietin 2 (Ang2) and VEGF shows promise for treating this diabetes complication.
Area of Science:
- Ophthalmology
- Endocrinology
- Vascular Biology
Background:
- Diabetic retinopathy (DR) is a major complication of diabetes, linked to poor glycemic control.
- The exact pathogenesis of DR is not fully understood, but involves vascular changes in the retina.
- Angiopoietins, particularly Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2), play critical roles in blood vessel regulation.
Purpose of the Study:
- To explore the role of angiopoietins in diabetic retinopathy pathogenesis.
- To investigate the therapeutic potential of targeting the angiopoietin system for DR treatment.
Main Methods:
- Review of recent advances in basic research on angiopoietins and their role in retinal vascularization.
- Analysis of the effects of Ang2 on human retinal endothelial cells, including VE-cadherin expression.
- Examination of vitreal Ang2 concentrations in patients with proliferative diabetic retinopathy and diabetic macular edema.
- Discussion of clinical trial results for Faricimab, a bispecific antibody targeting Ang2 and VEGF.
Main Results:
- Angiopoietin 2 (Ang2) destabilizes blood vessels, contrasting with Angiopoietin 1 (Ang1)'s stabilizing effect.
- Ang2 exposure reduces VE-cadherin expression in retinal endothelial cells, impairing cell-cell adhesion.
- Elevated vitreal Ang2 levels are observed in patients with proliferative diabetic retinopathy and diabetic macular edema.
- Faricimab, targeting both Ang2 and VEGF, demonstrates promising clinical outcomes in DR patients.
Conclusions:
- Angiopoietin 2 is implicated in the vascular pathology of diabetic retinopathy.
- Targeting Ang2, in combination with VEGF, represents a promising therapeutic strategy for managing diabetic retinopathy.
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