Sensing through Non-Sensing Ocular Ion Channels

Round 1

Reviewer 1 Report

This is a thorough review of ocular channelopathies by an emerging leader in the field. The manuscript is focused on channelopathies specifically associated with diseases of photoreceptors. There are a few grammar/usage errors peppered within the paper as to be expected with such an effort.  Manuscript is very thorough to the point of being unduly dense. The paper could use careful editing to be more succinct and concise. 

Minor usage and grammar notes:

line 14, overserved

line 41, identify fig number

line 45, epic? usage?

line 63, be consistent with abbreviations ie. Ca2+

line 66, fig number

line 98, extra /

line 149, "get" depolarized instead say are PR cells depolarize....

line 151, "on the expense..." change to "at the expense..."

line 183 extra space

line 281, replace till with to

line 327-330, remove italics

Author Response

We thank the reviewers for their time in diligently reviewing this manuscript and providing positive feed-back. We have made all changes as suggested and the manuscript reads much better now. Please find all suggested changes through our track change and provided table.

Reviewer 2 Report

Kabra and Pattnaik have done a great job by nicely summarizing the ocular channelopathies associated with mutations in several different ion channels and also discussed potential therapies.

Please consider the below minor comments:

1. The title should be adapted to include "ocular ion channels".
2. An introduction to electroretinogram a, b and c waves with a figure will prove helpful to a broader audience, given that this is discussed at multiple places in the review article.
3. Line 51 - Reference #11 seems inappropriate and rather a reference should be cited which describes the relevance of the mentioned channels in maintaining Ca²⁺ homeostasis in the lens.
4. Line 637 - point no. (3) Recently some flexibility in PAM has been reported (see Walton et al., Science 2020 and Chatterjee et al., Nat. Biotechnol. 2020) which might be worth mentioning briefly.

Please also fix the following:

1. Line 14 - "overserved" should be changed to "observed".
2. The number in the legend of Figure no. 1 is missing.
3. Line 52 - RPE should be expanded when using for the first time.
4. Line 98 - "assembly/ /trafficking/function" should be changed to "assembly/trafficking/function".
5. The number in the legend of Figure no. 2 is missing.
6. Line 159 - ERG should be expanded when used for the first time.
7. Line 227 - OPL and ONL should be expanded when using for the first time. Also please consider to show the OPL and ONL in figure 2.
8. Line 245 - "K+" should be changed to "K⁺".
9. Line 249 - "in once patient each" should be rephrased.
10. BVMD which is introduced in the text in line 507 should already be introduced in line 288.
11. Line 312 - Please change "Ca2+" to "Ca^2+"
12. Lines 327-330: Why Italicized?
13. Line 345 - "model has shown" to be changed to "models have shown".
14. Line 396 - "exhibited the exacerbated the" needs to be rephrased.
15. Lines 479-487: Why highlighted?
16. Line 538 - "P1" should be expanded to "postnatal day 1 (P1)".
17. Line 585 - "RPE-PR interface" should be expanded to "RPE-photoreceptor interface".
18. Line 728 - "Protein" should be changed to "protein".
19. Lines 730 and 735: "chaperons" should be changed to "chaperones"

Author Response

We thank the reviewer for the detailed comment which we have now addressed. The manuscript now is edited for language and all the recommended changes. We feel the manuscript reads much better now. We have included a table to direct to changes made and new line numbers. 

1. The title should be adapted to include "ocular ion channels".

Response: The title has been changed to “Sensing through Non-Sensing Ocular Ion Channels”

1. An introduction to electroretinogram a, b and c waves with a figure will prove helpful to a broader audience, given that this is discussed at multiple places in the review article.

Response: Along with the insertion of text details of a- and b-wave of ERG in section 2.2, an ERG figure showing the normal ERG and no b-wave is now included in figure 5.

1. Line 51 - Reference #11 seems inappropriate and rather a reference should be cited which describes the relevance of the mentioned channels in maintaining Ca²⁺ homeostasis in the lens.

Response: The reference has been edited to the relevant one.

1. Line 637 - point no. (3) Recently some flexibility in PAM has been reported (see Walton et al., Science 2020 and Chatterjee et al., Nat. Biotechnol. 2020) which might be worth mentioning briefly.

Response: The suggested studies have been included in section 4.1.2 (647-655 lines, references 276 and 277).