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Review
Peer-Review Record

Purinergic–Glycinergic Interaction in Neurodegenerative and Neuroinflammatory Disorders of the Retina

Int. J. Mol. Sci. 2021, 22(12), 6209; https://doi.org/10.3390/ijms22126209
by Laszlo G. Harsing, Jr. 1,*, Gábor Szénási 2, Tibor Zelles 1,3 and László Köles 1,3
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2021, 22(12), 6209; https://doi.org/10.3390/ijms22126209
Submission received: 25 May 2021 / Revised: 3 June 2021 / Accepted: 4 June 2021 / Published: 8 June 2021
(This article belongs to the Special Issue Purinergic Signaling in Neuroinflammation)

Round 1

Reviewer 1 Report

Dr. Laszlo G. Harsing, Jr. et al. presented a comprehensive, well-organized introduction containing metabolic mechanisms and clinic relevance in neurodegenerative and neuroinflammatory disorders of the retina. I did not have any major concerns, only several minor issues listed below:

 

  1. Please provide the scale bar for Figure 1A.
  2. Table 1 contains two tables, one is for introducing the drugs and another is for their full name, please label.
  3. Line 596, it seems that the sentence is incomplete.
  4. I suggest the authors could try to summarize the main feature in Part 4&5, like Figure 3 for Part 7.

Author Response

Referee 1 We appreciate the valuable comments of Referee 1.

Fig.1A. Scale bar is added to the figure.

The form of Table 1 is modified according to Referee’s suggestion.

The have checked the sentence in line 596.

An additional table (Table 3) is now added to link Parts 4 and 5.

Reviewer 2 Report

The authors have undertaken a fairly comprehensive review of neurodegenerative-neuroinflammatory disorders of the retina.  The authors concluded that the tripartite interaction between purinergic modulation, glutamatergic/glycinergic neurotransmission, and microglia activation provides three therapeutic targets, such as glycine transporter 1 inhibitors, P2Y purinoceptor agonists and P2X purinoceptor antagonists, and microglia inhibition by minocycline.  I have some comments that I believe need to be addressed prior to publication of this article.

 

Comments:

Page 8 lines 164–167, “The response of P2X purinoceptors to ATP mediates fast excitatory neurotransmission as their activation induces an inward-directed K+ current and cellular membrane depolarization [34,48].”  Generally, activation of K+ currents induce membrane hyperpolarization.  The P2X ionotropic purinoceptors are non-selectively permeable to cation.  Thus, the activation of P2X purinoceptors induces an inward-directed cation current.

Page 10 lines 387–389, “Suppression of the inflammatory cascade C-Raf/ERK by A2A receptor activation may be involved in the latter effect in microglia (Guzman-Aranguez et al., 2014).”, Please show the reference number.

Page 11 line 402, “P2Y11* purinoceptors alsomediate stimulation of adenylyl cyclase activation.”, Please revise this sentence.

Author Response

Referee 2 We thank Referee2 for the constructive comments.

Page 8, lines 164-167. Sentence is corrected as was suggested: inward-directed cation current.

Page 10, lines 367-389. Reference Guzman-Aranguez is numbered in page 10 para 4.

Page 11, linel 402. Table 2. footnote is corrected.

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