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It has been shown that flickering light can affect the development of eyeballs. However, the exact mechanism remains unclear. The ERK1/2-MMP-2 pathway is a classic pathway involved in the modulation of the extracellular matrix (ECM) in cancer tissues. However, to the best of our knowledge, the role of this pathway in modulating the scleral ECM in myopia has not been previously examined. The present study aimed to determine the effects of the ERK1/2-MMP-2 pathway on the formation of flickering light-induced myopia (FLM). Guinea pigs were raised under illumination at a flash rate of 0.5 Hz for 6 weeks to induce FLM. Peribulbar injections of dimethylsulfoxide or PD98059 (an inhibitor of phospho-ERK1/2) were administered starting at the third week of FLM modeling. Refraction was measured prior to and following treatments. The thickness of the posterior sclera (PS) was measured under a light microscope following H&E staining. The mRNA levels of MMP-2 were detected by the reverse transcription-quantitative PCR assay. The expression levels of MMP-2 and ERK1/2 were assayed by western blot and immunohistochemical analyses. Following 6 weeks of treatment, the refraction of the FLM group became more myopic compared with that of the control group, while PD98059 treatment inhibited the changes noted in the refraction. A marked reduction in the thickness of PS was observed in the FLM group, while PD98059 inhibited the remodeling of PS. In addition, the expression levels of MMP-2 and protein levels of phospho-ERK1/2 were increased in the FLM group, while PD98059 significantly inhibited MMP-2 mRNA and protein levels. These results indicated that ERK1/2-MMP-2 may be involved in the formation of FLM in guinea pigs by regulating the remodeling of PS.

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Purpose To evaluate the time trend of axial length (AL) and associated factors in 4- and 5-year-old children in Shanghai from 2013 to 2019. Methods This was a 7-year observational study of 985 four-year-old and 1059 five-year-old children in Shanghai. AL, horizontal and vertical corneal curvature, spherical equivalent (SE), and body height and weight were measured. Furthermore, a questionnaire was collected, including time outdoors and bad eyesight habits. Results In 4-year-old children, no significant difference was found in AL (P = 0.526), but significant differences were observed in SE (P = 0.001), horizontal corneal curvature (P = 0.006), vertical corneal curvature (P = 0.004), height (P < 0.001), and weight (P = 0.022) from 2013 to 2019. In 5-year-old children, no significant differences were found in AL (P = 0.304), SE (P = 0.200), or weight (P = 0.292), but significant differences were observed in horizontal corneal curvature (P = 0.040), vertical corneal curvature (P = 0.015), and height (P < 0.001) from 2013 to 2019. Multivariate analyses revealed that AL was mainly significantly associated with boys and time outdoors in the 4- and 5-year-old children. Conclusions The AL of 4- and 5-year-old children remained relatively stable in Shanghai from 2013 to 2019. Longitudinal studies are needed to confirm the relationship between AL elongation and environmental risk factors.

Previous studies have found that amphiregulin (AREG) may participate in eye elongation during the development of myopia, but the mechanism remains unclear. Here, we tested tear concentrations of AREG in adults and detected the role of AREG in scleral remodeling in form‐deprivation myopia (FDM) in guinea pigs. We found the tear concentrations of AREG in myopes were significantly higher than those in emmetropes using enzyme‐linked immunosorbent assay (ELISA). Tear concentrations of AREG were negatively correlated with spherical equivalent refraction and positively correlated with axial length (AL) and AL/corneal radii. We then used RNAi, DNA transfection and PD98059 treatments to determine the effects of AREG on extracellular signal‐regulated kinase 1/2 (ERK1/2) and matrix metalloprotease‐2 (MMP‐2) in primary scleral fibroblasts (SFs). The hypothesis was further verified via loss‐ and gain‐of‐function experiments by intravitreal application of anti‐AREG antibody (anti‐AR) or AREG in form‐deprivation eyes in guinea pigs. Immunofluorescence assay was used for cell type identification. Western‐blot and q‐PCR were used for the detection of relative expressions. Transmission electron microscopy was performed for posterior scleral observation. In vitro, we found AREG overexpression increased phospho‐ERK1/2 and MMP‐2 expression, while depletion of AREG inhibited their expressions. PD98059 (an effective ERK1/2 inhibitor) inhibited AREG‐induced MMP‐2 upregulation. In vivo, we found anti‐AR treatments suppressed FDM by inhibiting scleral remodeling, while AREG treatments promoted FDM. Our results suggest that AREG in tear fluids can serve as a potential biomarker in myopes. AREG is involved in scleral remodeling through the ERK1/2‐MMP‐2 pathway. AREG is a potential target for myopia control.