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Updated: Sep 30, 2025
Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits
Published on: June 2, 2019
siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats
Sandra Edith Cabrera-Becerra1, Gerardo Vera-Juárez2, Vanessa Giselle García-Rubio1
1Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, Mexico.
Abstract:
Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used. Diabetes was induced by a single dose of streptozotocin (STZ, 60 mg/kg i.p.). The siRNAs were designed, synthesised, and administered intravitreally at the beginning of diabetes induction (t0), and after 4 weeks of diabetes evolution (t4), subsequently evaluated the retinal neovascularization (junctions and lacunarity) and ANGPT2 expression in the retina by RT-PCR, after 4 weeks of the siRNAs administration. The results showed that the administration of STZ produced significant increases in blood glucose levels, retinal neovascularization (augmented junctions and lower lacunarity), and ANGPT2 expression, while the administration of the ANGPT2-siRNAs at different groups (t0 and t4) reduces the junctions and increases the lacunarity in diabetic rats. Therefore, we conclude that the administration of siRNAs targeting ANGPT2 could be an option to decrease the retinal neovascularization associated with PDR and halt the progression of blindness caused by diabetes.
Insights
This study shows that targeting angiopoietin 2 (ANGPT2) with siRNA can reduce retinal neovascularization in diabetic rats, offering a potential treatment for proliferative diabetic retinopathy (PDR) and preventing diabetes-related blindness.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes, characterized by abnormal blood vessel growth in the retina.
- This neovascularization is driven by the overexpression of angiogenic factors, notably angiopoietin 2 (ANGPT2).
Purpose of the Study:
- To design and evaluate the efficacy of small interfering RNA (siRNA) targeting ANGPT2 to inhibit retinal neovascularization in a rat model of diabetes.
- To assess the impact of ANGPT2 inhibition on key markers of PDR and ANGPT2 expression in the retina.
Main Methods:
- Diabetes was induced in adult male Wistar rats using streptozotocin (STZ).
- Synthesized ANGPT2-targeting siRNAs were administered intravitreally at two time points: at diabetes induction (t0) and 4 weeks post-induction (t4).
- Retinal neovascularization (junctions and lacunarity) and retinal ANGPT2 expression were quantified using RT-PCR after 4 weeks of siRNA treatment.
Main Results:
- STZ-induced diabetes significantly increased blood glucose levels, retinal neovascularization (higher junctions, lower lacunarity), and ANGPT2 expression.
- Intravitreal administration of ANGPT2-siRNAs effectively reduced retinal neovascularization, indicated by decreased junctions and increased lacunarity in diabetic rats.
- ANGPT2-siRNA treatment also led to a reduction in ANGPT2 expression in the retina.
Conclusions:
- siRNA-mediated silencing of ANGPT2 is a promising therapeutic strategy to mitigate retinal neovascularization in PDR.
- This approach holds potential for halting the progression of vision loss associated with diabetic retinopathy.
- Targeting ANGPT2 offers a novel avenue for managing sight-threatening complications of diabetes.
