IMR Press / FBL / Volume 28 / Issue 2 / DOI: 10.31083/j.fbl2802027
Open Access Original Research
Up-Regulation of NLRP3 in the Sclera Correlates with Myopia Progression in a Form-Deprivation Myopia Mouse Model
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1 Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China
2 Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, 100730 Beijing, China
*Correspondence: (Qin Long)
Front. Biosci. (Landmark Ed) 2023, 28(2), 27;
Submitted: 25 September 2022 | Revised: 9 December 2022 | Accepted: 13 December 2022 | Published: 8 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) is a common inflammatory factor that induces inflammation by increasing the expression of related cytokines. Although the NLRP3 inflammasome has been implicated in many ophthalmic diseases, its role in myopia is largely unknown. The aim of this study was to explore the relationship between myopia progression and the NLRP3 pathway. Methods: A form-deprivation myopia (FDM) mouse model was used. Different degrees of myopic shift were achieved via monocular form deprivation with 0-, 2-, and 4-week covering, and by 4-week covering followed by 1-week uncovering (the blank, FDM2, FDM4, and FDM5 groups, respectively) in both wild-type and NLRP3 (-/-) C57BL/6J mice. Axial length and refractive power were measured to assess the specific degree of myopic shift. The protein levels of NLRP3 and of related cytokines in the sclera were evaluated by Western blotting and immunohistochemistry. Collagen I and matrix metalloproteinase-2 (MMP-2), which affect extracellular matrix (ECM) remodeling of the sclera, were also examined to clarify the possible underlying mechanism. Results: In wild-type mice, the FDM4 group had the most significant myopic shift. Both the increase in refractive power and the elongation in axial length were significantly different between the experimental and control eyes in the FDM2 group. The protein levels of NLRP3, caspase-1, IL-1β, and IL-18 were significantly up-regulated in the FDM4 group compared to the other groups. The myopic shift was reversed and there was less up-regulation of cytokines in the FDM5 group compared to the FDM4 group. MMP-2 expression showed similar trends to NLRP3, while collagen I expression was inversely correlated. Similar results were found in NLRP3 -/- mice, although there was less myopic shift and less obvious changes in cytokine expression in the treatment groups as compared to the wild-type mice. In the blank group, no significant differences were found in refraction and axial length between wild-type mice and NLRP3 -/- mice of the same age. Conclusions: NLRP3 activation in the sclera could be involved in myopia progression in the FDM mouse model. Activation of the NLRP3 pathway up-regulated MMP-2 expression, which in turn affected collagen I and caused scleral ECM remodeling, eventually affecting myopic shift.

81870685/National Natural Science Foundation of China
7172173/Natural Science Foundation of Beijing Municipality
Fig. 1.
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