Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions
, Jamie Jiin-Yi Chen 2, Min Hu 3, Peng-Tai Tien 2,4, Hui-Ju Lin 2,5, Gezhi Xu 1,6,7, Lei Wan 5,8,9,* and Dekang Gan 1,*
Round 1
Reviewer 1 Report
This paper is based on a series of studies reported by the authors' group and attempts to show experimentally using tree shrews that the spillover of an inflammatory response into the eye may ultimately lead to a prolongation of the ocular axis, or myopia progression, through the cooperation of inflammatory cytokines. Although this is an interesting study, the authors need to make some modifications. The points are described in the followings.
1. Why does inflammation occur in a myopia model in which the eyelid is sutured shut? If this is the case, the question of whether inflammation causes ocular axis elongation or ocular axis elongation causes inflammation will not be resolved, and the authors' logic will lack persuasiveness. The authors need more explanation.
2. The immunohistochemistry picture (Fig. 3) shows MMP-2, COL-1, and NFκB only in the neural retina, not in the choroid or sclera. According to the authors' logic, since these proteins are involved in scleral collagen reorganization, their expressions should also be shown in the sclera. This would also require further presentations and discussion.
3. In Fig. 1a, there is an entry for FDM28 instead of FDM7, but FDM28 does not appear in the text and its meaning is unclear.
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This manuscript utilizes the tree shrew model for myopia development and uses form deprivation myopia (FDM) for 7 and 14 days. Twenty-one tree shrews were randomly assigned to 7 day and 14 day FDM by suturing one eye shut.
My main criticism is that tree shrews are generally not myopic, and these specific tree shrews were definitely not myopic. In the 7 day FDM group the Form Deprived eye went from +6.6 D to +4.0 D which is high hyperopia to less high hyperopia. In the 7 day FDM group the Form Deprived eye went from +6.5 D to +5.0 D which is high hyperopia to less high hyperopia, and it is interesting that 14 day form deprivation resulting in a lessening of the decrease in myopia (7 day, -2.4 D; 14 day, -1.5 D change). Granted, the change was in the direction of less hyperopia which could be described as a myopic shift, I suppose. But I find it remarkable that we're utilizing a mammal that does not have myopia to study myopia. At the very least this needs to be acknowledged, discussed, and explained that FD resulted in a lessening of hyperopia, or an increase in vitreous chamber depth and axial length which are generally associated with myopic development, but again in this case in tree shrews which are not myopic.
In line 255, the authors discuss near work but in general near work has only been weakly associated with myopia progression and is confounded by an association with spending less time outdoors. In fact, the association between spending time outdoors and myopia development is much more robust. If the authors are going to introduce the weak argument for near work, perhaps they should address the more robust and less controversial association with myopic children spending less time outdoors or in bright light.
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The comments that I had raised in the previous review were approximately responded and the manuscript is improved enough to be published.
