Alteration of retinal metabolism and oxidative stress may implicate myopic eye growth: Evidence from discovery and targeted proteomics in an animal model

Yu, Fu-Lai; Lam, Thomas Chuen; Sze, Andes Y.H.; Li, King Kit; Chun, Rachel Ka Man; Shan, Sze Wan; To, Chi Ho

doi:10.1016/j.jprot.2020.103684

Cited by 25 publications

(18 citation statements)

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“…In a cancer study, the increased regulation of PKM2 suggested enhanced glycolysis for tumor cells in vivo (Christofk et al, 2008). In addition, an increased level of PKM2 was also reported in chick retina study which compared LIM to LIH (Yu et al, 2020). The current study also found a decreased level of PKM in atropinetreated FDM guinea pigs, confirming the vital role of PKM in both LIM and FDM animal models.…”

Section: Pathway and Protein Interaction Analysis Of 29 Commonly Regulated Proteins In Itraq And Sequential Window Acquisition Of All Thesupporting

confidence: 85%

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

Zhu

Bian

et al. 2022

Front. Pharmacol.

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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.

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Section: Pathway and Protein Interaction Analysis Of 29 Commonly Regulated Proteins In Itraq And Sequential Window Acquisition Of All Thesupporting

confidence: 85%

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

Zhu

Bian

et al. 2022

Front. Pharmacol.

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“…Animal specimens are easier to obtain than clinical samples, and the amount of analyte is larger. While proteomic analyses of human specimens were limited to vitreous [10,32] and aqueous humor [19,26,28], other materials, such as sclera [22,23], retina [17] and cornea [12], were also included in animal studies. Both studies in humans and those involving animal models can be divided into non-targeted and targeted analyses.…”

Section: Proteomicsmentioning

confidence: 99%

“…In turn, chemical tags found application in the analysis of the proteomic profiles of the retina, vitreous and aqueous humor. Isotope-coded protein label (ICPL) was used in the studies of chick retina and vitreous humor [17,18], whereas iTRAQ was applied to analyze aqueous humor from patients with cataract [19,26] and atropine-treated mice with myopia [20]. While the latter analysis used the DDA approach, the SWATH analyses, especially those aimed at the creation of spectral libraries, involved the DIA approach.…”

Section: Proteomicsmentioning

confidence: 99%

“…Furthermore, this method was also used to analyze human tears in patients wearing orthokeratology lenses as myopia treatment [9]. The targeted approach, especially multiple reaction monitoring (MRM), was also used in the analysis of the retina from chicks with one myopic and one hyperopic eye [17]. Similar analyses were also performed on pig retina [24,30].…”

Section: Proteomicsmentioning

confidence: 99%

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Omics in Myopia

Grochowski

Pietrowska

Kowalczyk

et al. 2020

JCM

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Myopia is a globally emerging issue, with multiple medical and socio-economic burdens and no well-established causal treatment thus far. A better insight into altered biochemical pathways and underlying pathogenesis might facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the metabolomics and proteomics of myopia in humans and present various experimental approaches and animal models, along with their strengths and weaknesses. We also discuss the potential applicability of these findings to medical practice and suggest directions for future research.

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“…Working solutions of 100–500 nM atropine were freshly prepared from the stock and kept at 4°C before use. The sample preparation was similar to the metabolomics protocol, with few modifications for the retina samples (Paris et al, 2016 ; Yu et al, 2020 ). The retinas were placed in a 2-ml tube pre-packed with 1.4–2.8-mm ceramic beads in 200 μl methanol (CKMix, Precellys, Bertin Technologies, France), followed by homogenization at 5,800 rpm for four cycles of 30 s with 20-s intervals using a Precellys Evolution Tissue Homogenizer.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Low-Dose Atropine on Alpha Ganglion Cell Signaling in the Mouse Retina

Wang

Banerjee

et al. 2021

Front. Cell. Neurosci.

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Low-dose atropine helps to control myopia progression with few side effects. However, the impact of atropine, a non-selective muscarinic Acetylcholine (ACh) receptor antagonist, on retinal ganglion cells (RGCs) remains unclear. After immersing the cornea and adjacent conjunctiva of enucleated eyes in 0.05% (approximately 800 μM) atropine solution for 30 min, the atropine concentration reached in the retina was below 2 μM. After direct superfusion of the retina with 1 μM atropine (considering that the clinical application of 0.05% atropine eye drops will be diluted over time due to tear flow for 30 min), no noticeable changes in the morphology of ON and OFF alpha RGCs (αRGCs) were observed. Atropine affected the light-evoked responses of ON and OFF αRGCs in a dose- and time-dependent fashion. Direct application of less than 100 μM atropine on the retina did not affect light-evoked responses. The time latency of light-induced responses of ON or OFF αRGCs did not change after the application of 0.05–100 μM atropine for 5 min. However, 50 μM atropine extended the threshold of joint inter-spike interval (ISI) distribution of the RGCs. These results indicated that low-dose atropine (<0.5 μM; equal to 1% atropine topical application) did not interfere with spike frequency, the pattern of synchronized firing between OFF αRGCs, or the threshold of joint ISI distribution of αRGCs. The application of atropine unmasked inhibition to induce ON responses from certain OFF RGCs, possibly via the GABAergic pathway, potentially affecting visual information processing.

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Alteration of retinal metabolism and oxidative stress may implicate myopic eye growth: Evidence from discovery and targeted proteomics in an animal model

Cited by 25 publications

References 54 publications

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

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

Omics in Myopia

The Effect of Low-Dose Atropine on Alpha Ganglion Cell Signaling in the Mouse Retina

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