AREG is involved in scleral remodeling in form-deprivation myopia via the ERK1/2-MMP-2 pathway.
FASEB J
; 36(5): e22289, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35436023
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 2 da Matriz
/
Miopia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article