TY - JOUR
T1 - siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats
AU - Cabrera-Becerra, Sandra Edith
AU - Vera-Juárez, Gerardo
AU - García-Rubio, Vanessa Giselle
AU - Ocampo-Ortega, Sergio Adrián
AU - Blancas-Napoles, Citlali Margarita
AU - Aguilera-Méndez, Asdrubal
AU - Romero-Nava, Rodrigo
AU - Huang, Fengyang
AU - Hong, Enrique
AU - Villafaña, Santiago
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Angiopoietin 2
KW - Small interfering RNA
KW - proliferative diabetic retinopathy
KW - retinal neovascularization; blindness
UR - http://www.scopus.com/inward/record.url?scp=85127196769&partnerID=8YFLogxK
U2 - 10.1080/1061186X.2022.2052888
DO - 10.1080/1061186X.2022.2052888
M3 - Artículo
C2 - 35289235
AN - SCOPUS:85127196769
SN - 1061-186X
VL - 30
SP - 673
EP - 686
JO - Journal of Drug Targeting
JF - Journal of Drug Targeting
IS - 6
ER -