PONE-D-20-37537

Fatty acid-binding protein 4 is an independent factor in the pathogenesis of retinal vein occlusion

PLOS ONE

Dear Dr. Ida,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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- https://www.hindawi.com/journals/joph/2019/5185128/

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I congratulate the Authors, the study was performed, with correct scientific method, and appropriate qualitative method.

The research data has been collected in a way aimed at the purpose of the research, and they sufficiently support the results.

Therefore, the research results are relevant and useful in directing future research to address the treatment and pathogenesis of retinal vein occlusiono and its complications with the suppression of the FABP4 levels, with the use of statins, drugs agents, dipeptidyl peptidase 4 inhibitors (DPP4i) and angiotensin the II receptor blockers (ARB)

The results of the present study could help give new perspectives on the subject in terms of impact on current practice.

Introduction

I recommend adding the following references to line 5 Pag. 4:

…… agents substantially improved ME and visual acuity (VA) (7

Pacella F, La Torre G, Basili S, et al. Comparison between "early" or "late" intravitreal injection of dexamethasone implant in branch (BRVO) or central (CRVO) retinal vein occlusion: six-months follow-up. Cutan Ocul Toxicol. 2017 Sep;36(3):224-230. doi: 10.1080/15569527.2016.1254648. Epub 2017 Jan 11. PMID: 27903073.

line 7 Pag. 4:

………. even though VA and ME are improved (10

Pacella E, Pacella F, La Torre G, et al. Testing the effectiveness of intravitreal ranibizumab during 12 months of follow-up in venous occlusion treatment. Clin Ter. 2012 Nov;163(6):e413-22. PMID: 23306756.

I recommend adding the following references to line 10 Pag. 4:

………. risk factor for RVO (1,

Romiti GF, Corica B, Borgi M, Visioli G, Pacella E, Cangemi R, Proietti M, Basili S, Raparelli V. Inherited and acquired thrombophilia in adults with retinal vascular occlusion: A systematic review and meta-analysis. J Thromb Haemost. 2020 Aug 17. doi: 10.1111/jth.15068. Epub ahead of print. PMID: 32805772.

Pacella F, Bongiovanni G, Malvasi M, Trovato Battagliola E, Pistone A, Scalinci SZ, Basili S, La Torre G, Pacella E. Impact of cardiovascular risk factors on incidence and severity of Retinal Vein Occlusion. Clin Ter. 2020 Nov-Dec;171(6):e534-e538. doi: 10.7417/CT.2020.2269. PMID: 33151253.

Stefanutti C, Mesce D, Pacella F, et al. Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis. Atheroscler Suppl. 2019 Dec;40:49-54. doi: 10.1016/j.atherosclerosissup.2019.08.031. PMID: 31818450.

Bianchi E, Scarinci F, Ripandelli G, Feher J, et al. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis. Int J Mol Med. 2013 Jan;31(1):232-42. doi: 10.3892/ijmm.2012.1164. Epub 2012 Oct 26. PMID: 23128960.

Reviewer #2: 1)Summary

The paper is appropriate in content and the research question is good. The aim of the work was to identify the fatty acid-binding protein 4 (FABP4) expressed in both adipocytes and macrophages in vitreous fluid from patients with retinal vein occlusion (RVO). The levels of FABP4 and VEGFA, ocular blood flow by laser speckle flow graphy (LSFG), height and weight, systemic blood pressures and several blood biochemistry values were collected and analyzed. The levels of V-FABP4 and V-VEGFA were higher in RVO patients compared to the non-RVO patients. The MA, MV and MV-MT were significantly decreased in CRVO patients. The correlations were observed between Log VFABP4 and Log V-VEGF, Log VFABP4 and MV-MT at post-operative 1-week, Log VFABP4 and blood urea nitrogen. The MV-MT at post-operative 1week was independently associated with Log V-FABP4 after adjustment for age and gender, and gender. The Log V-FABP4 were independently associated with Log V-VEGFA after adjustment for age.

While on the whole the paper is readable, some grammar should be checked and rewritten, and professional English language editing is required.

2)Results

Please pay attention to number, grammar and spelling mistakes, such as patients with RVO (n=20), GTP. This sentence” and ALT, GTP and hsCRP, and LSFG ocular blood folw indexes including MA” was showed as a picture format, which should be revised. In Table 1, the MT data should be checked.

3)Discussion

I would suggest rewriting the discussion section, especially second half of first paragraph which should not only repeat the results section. In addition, correlation between FABP4 and LSFG mean blur rate (MBR) values of ONH should be more discussed.

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Reviewer #1: No

Reviewer #2: No

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Fatty acid-binding protein 4 is an independent factor in the pathogenesis of retinal vein occlusion

PONE-D-20-37537R1

Dear Dr. Ida,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Alfred S Lewin, Ph.D.

Section Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: (No Response)

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: (No Response)

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No