Table 2.

Details of included animal studies with induced myopia, such as animal model used (column A), proteomics technique (column B), identified DAPs (column C), and signaling pathways identified in the publication (column D). DAPs underwent IPA analysis to confirm existing and/or predict new significant signaling pathways affected in myopia (column E), with a p-value of < 0.05 for all pathways.

(A) Animal model	(B) Proteomics technique	(C) Identified DAPs	(D) Signaling Pathways identified in publication	(E)b The top categories of the most significant pathways identified in myopic eyes after IPA analysis
(1) Retina, Pigmented guinea pig, Started treatment from 4 days of age, 4D lenses on one eye for 8 days71	Fluorescence 2D-GE	8 proteins were identified by MS: β-actin, enolase 1, cytosolic malate dehydrogenase, protein-l-isoaspartate (D-aspartate) O-methyltransferase, PKM2 protein, X-linked eukaryotic translation initiation factor 1A, Ras-related protein Rab-11B, ACP1 protein	No signaling pathways were speculated. (Specific biological functions of identified, differentially expressed protein spots are described one by one.)	Biosynthesis: more energy-producing oxidation reactions Cellular immune response: more signaling pathways involved, including crosstalk between immune cells Neurotransmitter signaling: actin-based motility Intercellular and second messenger signaling: EIF2 signaling, RHOA signaling Growth factor signaling: FDGF and VEGF signaling
(2) Retina, Chick, 10D lenses on right eyes and + 10D lenses on left eyes for 3 and 7 days, respectively72	nano LC–ESI–MS/MS	PRDX6, GSTM2, APOA-I, VIM, IRBP, PKM, GAPDH, ENO1, LDHA	No signaling pathways were speculated. Specific function, and involved biological process of identified, differentially expressed proteins, are described one by one	Biosynthesis: Heparan Sulfate, Dermatan Sulfate, Chondroitin Sulfate Intercellular and second messenger signaling: lipid metabolites involved in immune regulation, such as Eicosanoid Signaling, Apelin Adipocyte Signaling Pathway Cellular stress and injury: hypoxia and HIF1α signaling pathway
(3) Retina, Pigmented guinea pig, Started treatment at 4 days of age, 5D lenses on one eye for 4 days36	Discovery: SWATH-MS; Protein validation: Multiple Reaction Monitoring assay; IPA	3202 nonredundant proteins were identified at 1% FDR Levels of 58 proteins were significantly changed after LIM treatment SLC6A6 and PTGES2 were validated	Using IPA, “lipid metabolism” was found as the main function associated with the differentially expressed proteins	Biosynthesis: inflammation relevant fatty acid metabolism Cellular immune response: PTGES2 involved pathway Neurotransmitters signaling: actin-based motility Intercellular and second messenger signaling: calcium signaling
(4) Retina, Albino guinea pig, Started treatment at 5 days of age, FDM for 4 weeks22	2D-GE; validation: MALDI-TOF	β-soluble NSF attachment protein; Phosphoglycerate mutase 1; VIM; Septin-6; Fascin 1; Collapsin response mediator protein-2A (Dihydropyrimidinase- Related Protein 2 DRP2); Succinate dehydrogenase complex subunit A; Preproalbumin	No signaling pathways were speculated. Reported proteins’ functions one by one, according to GeneOntology;	Biosynthesis: carbohydrate metabolism and biosynthesis of its regulator Cellular immune response: more signaling pathways involved, including nitric oxide pathway Nuclear receptor signaling: LXR/RXR and FXR/RXR activation Apoptosis: 14-3-3-mediated signaling and tight junction signaling Organismal growth and development: through post-transcriptional changes
(5) Retina, Pigmented guinea pig, Started treatment at 21 days of age, FDM for 4 weeks73	First stage: fractionated iTRAQ, coupled with nano-LC–MS/MS Second stage: label-free SWATH-MS Alpha-synuclein was verified using immunohisto-chemistry and confocal imaging	29 confident proteins at 1% FDR, comprising 12 up-regulated and 17 down-regulated proteins The most significantly regulated proteins were closely connected to Alpha-synuclein	Bioinformatics analysis using IPA and STRING databases identified signaling: EIF2 signaling; glycolysis; and dopamine secretion	Biosynthesis: phosphatidylglycerol biosynthesis II, CDP-diacylglycerol biosynthesis I, D-myo-inositol (1,4,5)-trisphosphate biosynthesis Cellular stress and injury: nucleotide excision repair pathway Cellular growth, proliferation and development of transcriptional and translational regulation: assembly of RNA polymerase II complex, mTOR signaling, regulation of elF4 and p70S6K signaling, sumoylation pathway, EIF2 signaling
(6) Combined retina, RPE and choroid, Tilapia, Started treatment at 3 months of age, FDM for 4 weeks31	2D-GE and MS A total of 18 protein spots separated	Annexin A5, gelsolin, and chaperonin-containing TCP-1 (CCT) are downregulated	No signaling pathways were speculated	Transport: calcium transport I Cellular growth, proliferation and development: bone remodeling and development and activation of osteoclasts (possibly in the modulation of immune responses)34 Neurotransmitters and other nervous system signaling: Actin-based Motility Intercellular and second messenger signaling: integrin signaling
(7) Sclera, Pigmented guinea pigs, Started treatment at 2 weeks of age, FDM for 4 weeks74	iTRAQ labeling combined with LC − MS/MS GO and IPA were used to identify the proteins’ functions and networks involved	A total of 2,579 unique proteins with < 1% FDR were identified Levels of 56 proteins were increased, and those of 84 proteins were decreased, in FDM eyes Validated proteins: RhoA, myosin IIB, ACTIN 3, RAP1A	44 of 140 proteins differing in amount were involved in cellular movement and cellular assembly and organization Relevant pathways (GO BP): cellular process (GO: 0009987), single-organism process (GO: 0044699), metabolic process (GO: 0008152)	64 significantly different signaling pathways were identified and relevant to: Cellular immune response: activated Cellular stress and injury: activated Cytokine signaling: activated Biosynthesis: mainly cholesterol biosynthesis, the differences between myopic and control eyes are significant but the direction of change (activation vs. inhibition) was not reliably predictable by IPA analysis

^bThe top categories of the most significant pathways identified in myopic eyes after IPA analysis are listed in column E.