Proteomic evidence that ABCA4 is vital for traumatic proliferative vitreoretinopathy formation and development

• Published in: Experimental eye research 2019-04, Vol.181, p.232-239
• Main Authors: Wang, Menghua, Li, Qiuming, Dong, Hongtao
• Format: Article
• Language: English
• Subjects: ABCA4; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Blotting, Western; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; Eye Injuries - complications; Eye Injuries - metabolism; Eye Injuries - pathology; Female; Follow-Up Studies; Gene Expression Regulation; Humans; Male; Middle Aged; Migration; Ophthalmoscopy; Proliferation; Proliferative vitreoretinopathy (PVR); Proteomics; Retinal pigment epithelial (RPE) cells; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; Retrospective Studies; RNA - genetics; Rod Cell Outer Segment; Vitreoretinopathy, Proliferative - etiology; Vitreoretinopathy, Proliferative - genetics; Vitreoretinopathy, Proliferative - metabolism
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2019.02.006

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment failure. The mechanism of PVR development is complex and still not completely elucidated. There are no proven methods for early prevention or clinical treatment. Retinal proteins are abnormally expressed during the entire PVR disease process. Due to the limitations of research methods and techniques, we do not fully understand the retinal protein changes in PVR. This proteomics study systemically analyzed and identified differential protein expression between retinas of PVR and non-PVR (normal) eyes. Retinal samples were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) coupled with mass spectrometry. Raw data were processed and analyzed by Maxquant software and then searched against the human UniProKB (201510) protein database. Differentially expressed proteins were selected and further validated in a human retinal pigment epithelial (RPE) cell line. The effects of dysregulated proteins on cell proliferation, apoptosis, and migration were studied. Systemic proteomics analysis identified several PVR-enriched proteins. The differentially expressed proteins were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation to find abnormal pathways involved in PVR. Retinal-specific ATP-binding cassette transporter (ABCA4) expression was one of the most increased proteins in PVR tissue. ABCA4 knockdown significantly reduced proliferation and affected the cell cycle in the human RPE cell line. ABCA4 knockdown also induced apoptosis and inhibited retinal cell migration. In conclusion, systemic proteomics analysis identified differentially expressed proteins in traumatic PVR, with ABCA4 being highly expressed. Disruption of ABCA4 expression induced apoptosis and inhibited cell proliferation and migration in a human RPE cell line. •Differential expressed proteins in PVR were found by systemic proteomics analysis.•ABCA4 was highly expressed in PVR.•ABCA4 is indispensable in development of retinal degenerative diseases.