PONE-D-20-23950

Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.

PLOS ONE

Dear Dr. Shahidullah,

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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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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

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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: Shahidullah and colleagues studied the effects of terbutaline, forskolin and 8-Br-cAMP to elucidate involvement of cyclic AMP and intracellular Ca2+, [Ca2+]i, in the modulation of aqueous humour formation (AHF) in the isolated bovine eye and cultured ciliary epithelial cells. They found that AHF can be manipulated through cyclic AMP, operating via protein kinase A, which can affect [Ca2+]i homeostasis. In addition, calcium release from the intracellular store affects AHF, and interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion. The text is well written, and the interpretation of data are appropriate. Although there are not much surprises in the result, the data are regid. A few concerns exist.

Major concerns:

Although the authors claim that the effects of terbutaline and other drugs functioned dose-dependently, they did not except 8-Br cAMP in Fig. 1-3.

Minor concerns:

The formats of many articles in the reference list are incorrect. For instance, "Current eye research" should be "Curr Eye Res" in #12.

Reviewer #2: I have carefully read the article by Shahidullah et al. titled Terbutaline, forskolin and cAMP reduce the secretion of aqueous humor in the isolated bovine eye.

This article introduces us to the effect that terbutaline, forskolin and cAMP have on the production of aqueous humor in perfused bovine eyes. These substances induce a decrease in its production. Although the author does not conduct innovative experiments, forskolin is known to increase intracellular levels of cAMP, but perhaps it is less known that the β2 adrenergic receptor agonist (such as terbutaline) can have an antioxidant effect and today it is known that the glaucoma has a pathogenesis related to oxidative damage. So it would have been interesting to explore this possibility.However, in this article the only thing I disagree is the short title given by the authors to this article (as it has been known for over 30 years that Ca ++ is the second messenger in all cells and which also "exploits" the cyclic AMP). Therefore, I believe there is a small contradiction, it is not the effect of cyclic AMP that decreases the production of aqueous humor, and consequently the short title of the article: "Cyclic AMP reduces the secretion of aqueous humor" it's incorrect. While I agree with the authors when they state that: cAMP plays a role in modulating AH secretion. However, the article is well conducted. well-performed experiments and statistics are correct. So the only thing I would change is the short title to: Cyclic AMP modulates the production of aqueous humor.

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Reviewer #1: No

Reviewer #2: Yes: Sergio Claudio Saccà

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Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.

PONE-D-20-23950R1

Dear Dr. Shahidullah,

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.

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Kind regards,

Agustín Guerrero-Hernandez

Academic 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: (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

**********

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

Reviewer #1: Yes

**********

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

**********

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

**********

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)

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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.

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Reviewer #1: No