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The circRNA MKLN1 regulates autophagy in the development of diabetic retinopathy

Jiahui Yang1, Chengye Tan1, Yan Wang1

  • 1Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu 214023, People's Republic of China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|August 7, 2023
PubMed

Insights

Circular RNAs (circRNAs) like circMKLN1 are implicated in diabetic retinopathy (DR). Inhibiting circMKLN1 shows promise in treating DR by reducing retinal damage and vascular leakage.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Genetics

Background:

  • Diabetic retinopathy (DR) is a leading cause of blindness in working-age individuals.
  • The underlying mechanisms of DR remain incompletely understood.
  • Circular RNAs (circRNAs) are emerging as key regulators in disease pathogenesis via the competing endogenous RNA (ceRNA) model.

Purpose of the Study:

  • To investigate the role of circRNAs in diabetic retinopathy.
  • To identify specific circRNAs and their regulatory pathways involved in DR.
  • To explore potential diagnostic biomarkers and therapeutic targets for DR.

Main Methods:

  • Serum extracellular vesicle total RNA isolation and deep sequencing from healthy controls and patients with diabetes mellitus (DM), nonproliferative DR (NPDR), and proliferative DR (PDR).
  • Streptozotocin (STZ)-induced mouse model of diabetes to assess circMKLN1 inhibition effects.
  • In vitro studies using human retinal microvascular endothelial cells (hRMECs) under high glucose (HG)/methylglyoxal (MG) conditions.
  • Investigated the interaction between circMKLN1, miR-26a-5p, and Rab11a.

Main Results:

  • Aberrantly high expression of circMKLN1 was detected in DR patients.
  • Inhibition of circMKLN1 in a mouse model ameliorated retinal acellular vessels and vascular leakage, effects reversible by rapamycin.
  • CircMKLN1 acts as a molecular sponge for miR-26a-5p, mediating HG/MG-induced autophagy and inflammation in hRMECs.
  • CircMKLN1-silencing reduced reactive autophagy and inflammation.
  • CircMKLN1 targets miR-26a-5p, influencing Rab11a expression.

Conclusions:

  • CircMKLN1 is significantly upregulated in diabetic retinopathy and contributes to its pathogenesis.
  • CircMKLN1 inhibition demonstrates therapeutic potential for DR by modulating autophagy and inflammation.
  • The circMKLN1/miR-26a-5p/Rab11a axis represents a novel regulatory pathway in DR.
  • CircMKLN1 holds promise as a potential biomarker and therapeutic target for diabetic retinopathy.
Keywords:
AutophagyDiabetic retinopathyRab11acircRNA

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