Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients

International Journal of Molecular Sciences

Ali Koskela¹  Kai Kaarniranta¹  Elisabeth Richert²  Alexa Klettner²  Heli Skottman³  Mostafa Kiamehr³  Kati Juuti-Uusitalo³  Katriina Aalto-Setälä³  Arto Koistinen⁴ 

[1] Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, Finland;Department of Ophthalmology, University of Kiel, University Medical Center, 24105 Kiel, Germany;Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland;SIB Labs, University of Eastern Finland, 70210 Kuopio, Finland;

关键词: retinal pigment epithelial cells;    type 2 diabetes;    diabetic retinopathy (DR);    induced pluripotent stem cells (hiPSC);    barrier function;    autophagy;    matrix metalloproteinase;   

DOI  :  10.3390/ijms20153773

来源: DOAJ

【 摘 要 】

In diabetic patients, high blood glucose induces alterations in retinal function and can lead to visual impairment due to diabetic retinopathy. In immortalized retinal pigment epithelial (RPE) cultures, high glucose concentrations are shown to lead to impairment in epithelial barrier properties. For the first time, the induced pluripotent stem-cell-derived retinal pigment epithelium (hiPSC-RPE) cell lines derived from type 2 diabetics and healthy control patients were utilized to assess the effects of glucose concentration on the cellular functionality. We show that both type 2 diabetic and healthy control hiPSC-RPE lines differentiate and mature well, both in high and normal glucose concentrations, express RPE specific genes, secrete pigment epithelium derived factor, and form a polarized cell layer. Here, type 2 diabetic hiPSC-RPE cells had a decreased barrier function compared to controls. Added insulin increased the epithelial cell layer tightness in normal glucose concentrations, and the effect was more evident in type 2 diabetics than in healthy control hiPSC-RPE cells. In addition, the preliminary functionality assessments showed that type 2 diabetic hiPSC-RPE cells had attenuated autophagy detected via ubiquitin-binding protein p62/Sequestosome-1 (p62/SQSTM1) accumulation, and lowered pro- matrix metalloproteinase 2 (proMMP2) as well as increased pro-MMP9 secretion. These results suggest that the cellular ability to tolerate stress is possibly decreased in type 2 diabetic RPE cells.

【 授权许可】

Unknown