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Title: | Alteration of EIF2 signaling, glycolysis, and dopamine secretion in form-deprived myopia in response to 1% atropine treatment : evidence from interactive iTRAQ-MS and SWATH-MS proteomics using a guinea pig model | Authors: | Zhu, Y Bian, JF Lu, DQ To, CH Lam, CSY Li, KK Yu, FJ Gong, BT Wang, Q Ji, XW Zhang, HM Nian, H Lam, TC Wei, RH |
Issue Date: | Jan-2022 | Source: | Frontiers in pharmacology, Jan. 2022, v. 13, 814814, p. 1-20 | Abstract: | Purpose: Atropine, a non-selective muscarinic antagonist, effectively slows down myopia progression in human adolescents and several animal models. However, the underlying molecular mechanism is unclear. The current study investigated retinal protein changes of form-deprived myopic (FDM) guinea pigs in response to topical administration of 1% atropine gel (10 g/L). Methods: At the first stage, the differentially expressed proteins were screened using fractionated isobaric tags for a relative and absolute quantification (iTRAQ) approach, coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) (n = 24, 48 eyes) using a sample pooling technique. At the second stage, retinal tissues from another cohort with the same treatment (n = 12, 24 eyes) with significant ocular changes were subjected to label-free sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics for orthogonal protein target confirmation. The localization of Alpha-synuclein was verified using immunohistochemistry and confocal imaging. Results: A total of 1,695 proteins (8,875 peptides) were identified with 479 regulated proteins (FC ≥ 1.5 or ≤0.67) found from FDM eyes and atropine-treated eyes receiving 4-weeks drug treatment using iTRAQ-MS proteomics. Combining the iTRAQ-MS and SWATH-MS datasets, a total of 29 confident proteins at 1% FDR were consistently quantified and matched, comprising 12 up-regulated and 17 down-regulated proteins which differed between FDM eyes and atropine treated eyes (iTRAQ: FC ≥ 1.5 or ≤0.67, SWATH: FC ≥ 1.4 or ≤0.71, p-value of ≤0.05). Bioinformatics analysis using IPA and STRING databases of these commonly regulated proteins revealed the involvement of the three commonly significant pathways: EIF2 signaling; glycolysis; and dopamine secretion. Additionally, the most significantly regulated proteins were closely connected to Alpha-synuclein (SNCA). Using immunostaining (n = 3), SNCA was further confirmed in the inner margin of the inner nuclear layer (INL) and spread throughout the inner plexiform layer (IPL) of the retina of guinea pigs. Conclusion: The molecular evidence using next-generation proteomics (NGP) revealed that retinal EIF2 signaling, glycolysis, and dopamine secretion through SNCA are implicated in atropine treatment of myopia in the FDM-induced guinea pig model. |
Keywords: | Atropine FDM Guinea pigs ITRAQ-MS Retina SWATH-MS |
Publisher: | Frontiers Research Foundation | Journal: | Frontiers in pharmacology | EISSN: | 1663-9812 | DOI: | 10.3389/fphar.2022.814814 | Rights: | Copyright © 2022 Zhu, Bian, Lu, To, Lam, Li, Yu, Gong, Wang, Ji, Zhang, Nian,
Lam and Wei. This is an open-access article distributed under the terms of the
Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal is
cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms. The following publication Zhu Y, Bian JF, Lu DQ, To CH, Lam CS-Y, Li KK, Yu FJ, Gong BT, Wang Q, Ji XW, Zhang HM, Nian H, Lam TC and Wei RH (2022) Alteration of EIF2 Signaling, Glycolysis, and Dopamine Secretion in Form-Deprived Myopia in Response to 1% Atropine Treatment: Evidence From Interactive iTRAQ-MS and SWATH-MS Proteomics Using a Guinea Pig Model. Front. Pharmacol. 13:814814 is available at https://doi.org/10.3389/fphar.2022.814814 |
Appears in Collections: | Journal/Magazine Article |
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