Blockade of Annexin A2 Prevents Early Microvasculopathy in Murine Models of Diabetic Retinopathy.

Abstract

Purpose:

We examined the role of annexin A2 (A2) in the development of diabetic retinal vasculopathy by testing the effect of Anxa2 gene deletion as well as administration of anti-A2 antibodies on pericyte dropout and retinal neovascularization in diabetic Akita mice, and in mice subjected to oxygen-induced retinopathy.

Methods:

We analyzed diabetic Ins2AKITA mice with or without global deletion of Anxa2, as well as Ins2AKITA mice that received intravitreal anti-A2 IgG or control antibody at 2, 4, and 6 months, for retinal pericyte dropout at 7 months of age. In addition, we assessed the effect of intravitreal anti-A2 on oxygen-induced retinopathy (OIR) in neonatal mice by quantifying retinal neovascular and vaso-obliterative area, and by enumeration of neovascular tufts.

Results:

Both deletion of the Anxa2 gene and immunologic blockade of A2 prevented pericyte depletion in retinas of diabetic Ins2AKITA mice. Blockade of A2 also reduced vaso-obliteration and neovascularization in the OIR model of vascular proliferation. This effect was amplified when a combination of antivascular endothelial growth factor (VEGF) and anti-A2 antibodies was used.

Conclusions:

Therapeutic approaches that target A2, alone or in combination with anti-VEGF therapy, are effective in mice, and may also curtail the progression of retinal vascular disease in humans with diabetes.

• Authors: Valentina Dallacasagrande, Wei Liu, Dena Almeida, Min Luo, Katherine A Hajjar
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 64 Issue 4 Pg. 33 (04 03 2023) ISSN: 1552-5783 [Electronic] United States
• PMID: 37103008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Annexin A2
• Oxygen
• Vascular Endothelial Growth Factor A
• Anxa2 protein, mouse

Topics

• Animals
• Mice
• Annexin A2 (genetics, metabolism, therapeutic use)
• Diabetes Mellitus
• Diabetic Retinopathy (prevention & control)
• Disease Models, Animal
• Mice, Inbred C57BL
• Oxygen (toxicity, metabolism)
• Retinal Diseases (metabolism)
• Retinal Neovascularization (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)