Exosomal microRNA-133b-3p from bone marrow mesenchymal stem cells inhibits angiogenesis and oxidative stress via FBN1 repression in diabetic retinopathy.

Diabetic retinopathy (DR) is a common microvascular complication. Many studies have focused on the role of microRNAs (miRNAs) in DR but not specifically on miR-133b-3p. Thus, this study is to unmask the mechanisms of miR-133b-3p in DR. KK/Upj-Ay mice (a spontaneous diabetic nephropathy model of DM, referred to as DR mice) were used in the study, and retinal tissues were collected. Bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. High glucose (HG)-treated mouse retinal microvascular endothelial cells (mRMECs) were transfected or co-cultured with BMSCs-derived exosomes. Then, cell proliferation, migration, apoptosis, angiogenesis, and oxidative stress were observed. MiR-133b-3p and FBN1 expression in tissues and cells was detected. MiR-133b-3p expression was reduced, and FBN1 expression was increased in retinal tissues of DR mice and HG-treated mRMECs. Up-regulating miR-133b-3p or down-regulating FBN1 or BMSCs-derived exosomes impaired oxidative stress, angiogenesis, proliferation, migration, and promoted apoptosis of HG-treated mRMECs. This study has elucidated that exosomal miR-133b-3p from BMSCs suppresses angiogenesis and oxidative stress in DR via FBN1 repression.

CircZNF532 knockdown protects retinal pigment epithelial cells against high glucose-induced apoptosis and pyroptosis by regulating the miR-20b-5p/STAT3 axis.

INTRODUCTION: The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells. MATERIALS AND METHODS: Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE-19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR-20b-5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established. RESULTS: CircZNF532 and STAT3 were upregulated but miR-20b-5p was downregulated in the serum samples of patients with DR and HG-induced ARPE-19 cells. Elevated miR-20b-5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE-19 cells. CircZNF532 sponged miR-20b-5p and inhibited its expression. STAT3 was verified as a target of miR-20b-5p. MiR-20b-5p modulated ARPE-19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ-induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR-20b-5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues. CONCLUSION: CircZNF532 knockdown rescued human RPE cells from HG-induced apoptosis and pyroptosis by regulating STAT3 via miR-20b-5p.