Effect of high glucose on secreted proteome in cultured retinal pigmented epithelium cells: its possible relevance to clinical diabetic retinopathy.
Retinopathy has been observed in around quarter of diabetic patients. Diabetic retinopathy can result in poor vision and even blindness since high glucose has been evidenced to weaken retinal capillary leading to leakage of blood into the surrounding space. In the present study, a proteomics-based approach has been applied to analyze a model retinal pigmented epithelium cell line, ARPE-19, grown in mannitol-balanced 5.5mM, 25 mM and 100 mM D-glucose culture media and used as a model for hyperglycemia secretomic analysis. Totally, 55 differentially secreted proteins have been firmly identified representing 46 unique gene products. These secreted proteins mainly function in cytoskeleton-associated adhesion/junction (such as galectin-3-binding protein) and transport (multidrug resistance-associated protein 1). Additionally, the identified secreted markers including asialoglycoprotein receptor 1, lysophosphatidic acid receptor 3, moesin, MPP2, haptoglobin and cathepsin D were further validated in plasma samples coming from type 2 diabetic patients with retinopathy and healthy donors. In summary, we report a comprehensive retinal cell-based proteomic approach for the identification of potential secreted retinal markers-induced in high glucose conditions. Some of these identified secreted proteins have been validated in diabetic retinopathy plasma demonstrating the potentially utilizing of these markers in screening and treating diabetic retinopathy.
Institute of Bioinformatics and Structural Biology & Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
You-Hsuan
YH
Chen
Hsiu-Chuan
HC
Chou
Szu-Ting
ST
Lin
Yi-Wen
YW
Chen
Yi-Wen
YW
Lo
Hong-Lin
HL
Chan
D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology*
D015415:Biomarkers; D005136:Eye Proteins; D020543:Proteome; D013549:Sweetening Agents; D005947:Glucose