Early phosphoproteomic changes in the retina following optic nerve crush.

Autor: Liu Y; Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: yang.liu@unthsc.edu., Zhong H; Shenzhen Eye Hospital, Shenzhen Key Laboratory of Ophthalmology, Ocular Trauma Treatment and Stem Cell Differentiation Public Service Platform of Shenzhen, Optometry College of Shenzhen University, Shenzhen, Guangdong, China., Bussan EL; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA., Pang IH; Department of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: iok-hou.pang@unthsc.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2020 Dec; Vol. 334, pp. 113481. Date of Electronic Publication: 2020 Sep 21.
DOI: 10.1016/j.expneurol.2020.113481
Abstrakt: Retinal ganglion cell (RGC) death causes irreversible blindness in adult mammals. Death of RGC occurs in diseases including glaucoma or injuries to the optic nerve (ON). To investigate mechanisms involved in RGC degeneration, we evaluated the phosphoproteomic changes in the retina induced by ON injury. Intraorbital optic nerve crush (ONC) was performed in adult C57BL/6J mice. Retinas were collected at 0, 6, and 12 h following ONC. Retinal proteins labeled with CyDye-C2 were subject to 2D-PAGE, followed by phosphoprotein staining and in-gel/cross-gel image analysis. Proteins with significant changes in phosphorylation (ratios ≥1.2) in retinas of the injured eyes compared to the control eyes were spot-picked, tryptic digested, and peptide fragments were analyzed by MALDI-TOF (MS) and TOF/TOF (tandem MS/MS). Intraorbital ONC increased phosphorylation of many retinal proteins. Among them, 29 significantly phosphorylated proteins were identified. PANTHER analysis showed that these proteins are associated with a variety of protein classes, cellular components, biological processes and signaling pathways. One of the identified proteins, phosphoprotein enriched in astrocytes 15 (PEA15), was further validated by western blotting and immunofluorescence staining. Functions of PEA15 were determined in cultured astrocytes. PEA15 knockdown reduced astrocyte phagocytic activity but promoted cell migration. Long term PEA15 knockdown also decreased astrocyte ATP level. This study provides new insights into mechanisms of RGC degeneration after ON injury, as well as central nervous system (CNS) neurodegeneration, since the retina is an extension of the CNS. These new insights will lead to novel therapeutic targets for retinal and CNS neurodegeneration.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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