siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats

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.

Keywords:

• Small interfering RNA
• Angiopoietin 2
• proliferative diabetic retinopathy
• retinal neovascularization; blindness

Author contributions

SEC and SV: concept and design. SEC, GV, VGG, SAO, CMB, AA, RR, FH, EH, and SV: data collection and processing. SEC, VGG, SAO, CMB, and SV: analysis and interpretation. SEC, VGG, SAO, CMB, AA, RR, FH, EH, and SV: literature research. SEC, GV, VGG, SAO, CMB, and SV: laboratory assays. All authors accept responsibility for the entire content of this submitted manuscript and have approved its submission.

Disclosure statement

The authors declare that there is no conflict of interest. The authors alone are responsible for the content and writing of the article.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research protocol was supported by grants from Secretaria de Investigación y Posgrado del Instituto Politécnico Nacional (Proyectos Insignia IPN-2015 and SIP-IPN: 20221282) and Cabrera-Becerra SE received a doctoral fellowship from CONACYT (418913).