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Open AccessArticle

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

1
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
2
Department of Ophthalmology, University of Kiel, University Medical Center, 24105 Kiel, Germany
3
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, Finland
4
SIB Labs, University of Eastern Finland, 70210 Kuopio, Finland
5
Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland
6
Department of Molecular Genetics, University of Lodz, 90-136 Lodz, Poland
7
Heart Hospital, Tampere University Hospital, 33521 Tampere, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3773; https://doi.org/10.3390/ijms20153773
Received: 18 June 2019 / Revised: 23 July 2019 / Accepted: 1 August 2019 / Published: 1 August 2019
(This article belongs to the Collection Feature Papers in Molecular Biology)
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. View Full-Text
Keywords: retinal pigment epithelial cells; type 2 diabetes; diabetic retinopathy (DR); induced pluripotent stem cells (hiPSC); barrier function; autophagy; matrix metalloproteinase retinal pigment epithelial cells; type 2 diabetes; diabetic retinopathy (DR); induced pluripotent stem cells (hiPSC); barrier function; autophagy; matrix metalloproteinase
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MDPI and ACS Style

Kiamehr, M.; Klettner, A.; Richert, E.; Koskela, A.; Koistinen, A.; Skottman, H.; Kaarniranta, K.; Aalto-Setälä, K.; Juuti-Uusitalo, K. Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients. Int. J. Mol. Sci. 2019, 20, 3773. https://doi.org/10.3390/ijms20153773

AMA Style

Kiamehr M, Klettner A, Richert E, Koskela A, Koistinen A, Skottman H, Kaarniranta K, Aalto-Setälä K, Juuti-Uusitalo K. Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients. International Journal of Molecular Sciences. 2019; 20(15):3773. https://doi.org/10.3390/ijms20153773

Chicago/Turabian Style

Kiamehr, Mostafa; Klettner, Alexa; Richert, Elisabeth; Koskela, Ali; Koistinen, Arto; Skottman, Heli; Kaarniranta, Kai; Aalto-Setälä, Katriina; Juuti-Uusitalo, Kati. 2019. "Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients" Int. J. Mol. Sci. 20, no. 15: 3773. https://doi.org/10.3390/ijms20153773

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