Blockade of Annexin A2 Prevents Early Microvasculopathy in Murine Models of Diabetic Retinopathy
Valentina Dallacasagrande1, Wei Liu1, Dena Almeida1
1Department of Pediatrics, Weill Cornell Medicine, New York, New York, United States.
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.
Insights
Targeting annexin A2 (A2) prevents diabetic retinal vasculopathy and oxygen-induced retinopathy in mice. Combining anti-A2 therapy with anti-VEGF shows amplified therapeutic effects.
Area of Science:
- Ophthalmology
- Vascular Biology
- Diabetic Complications
Background:
- Diabetic retinal vasculopathy is a leading cause of blindness.
- Pericyte loss and neovascularization are key pathological features.
- Annexin A2 (A2) is implicated in vascular disease development.
Purpose of the Study:
- To investigate the role of annexin A2 (A2) in diabetic retinal vasculopathy.
- To evaluate the therapeutic potential of targeting A2 in mouse models of retinopathy.
Main Methods:
- Assessed Anxa2 gene deletion and anti-A2 antibody administration in diabetic Akita mice.
- Studied the effect of anti-A2 on oxygen-induced retinopathy (OIR) in neonatal mice.
- Quantified pericyte dropout, neovascularization, and vaso-obliteration.
Main Results:
- Anxa2 gene deletion and anti-A2 blockade prevented pericyte loss in diabetic mice.
- Anti-A2 treatment reduced neovascularization and vaso-obliteration in OIR.
- Combination therapy with anti-VEGF and anti-A2 showed amplified effects.
Conclusions:
- Targeting A2 is a promising therapeutic strategy for diabetic retinal vasculopathy.
- Combined anti-A2 and anti-VEGF therapy may offer enhanced benefits.
- These findings suggest potential for A2-targeted therapies in human diabetic eye disease.
