TY - JOUR
T1 - Localization of the ultraviolet-sensor Opn5m and its effect on myopia-related gene expression in the late-embryonic chick eye
AU - Kato, Mutsuko
AU - Sato, Keita
AU - Habuta, Munenori
AU - Fujita, Hirofumi
AU - Bando, Tetsuya
AU - Morizane, Yuki
AU - Shiraga, Fumio
AU - Miyaishi, Satoru
AU - Ohuchi, Hideyo
N1 - Funding Information:
Egr1, also called ZENK or zif268, encodes a zinc finger transcription factor, which regulates transcription of genes involved in tissue remodeling and fibrosis. Its target genes include those of Tgf betas, collagens, Timps, and other growth factors and matrix proteins. Egr1 is one of the major mediators in fibroblasts or myofibroblasts not only in physiological tissue remodeling but also in pathological fibrosis. Egr1 was the first gene to be identified whose synthesis is enhanced when ocular elongation is suppressed [22], and Egr1-knockout mice exhibit axial eye growth [23]. However, all these alterations of Egr1 expression have been observed in the retina. Our study shows that UV-A reception through Opn5m in the presence of 11-cis-retinal significantly upregulates the expression of Egr1 in fibroblasts, which supports the possibility of a direct effect on the sclera or cornea by UV reception via Opn5m.We thank Dr. Takahiro Yamashita for his generous gift of 11-cis-retinal. We also thank Central Research Laboratory, Okayama University Medical School for allowing us to conduct the analysis of immunofluorescence using Zeiss LSM 780. This study was partly supported by an academic grant from Pfizer Japan Inc. and grants-in-aid from MEXT (24500382 to HO, 17K15159 to KS), Japan.
Publisher Copyright:
© 2019 The Authors
PY - 2019/9
Y1 - 2019/9
N2 - Recent studies show that exposure to ultraviolet (UV) light suppresses ocular elongation, which causes myopia development. However, the specific mechanisms of this process have not been elucidated. A UV-sensor, Opsin 5 (Opn5) mRNA was shown to be present in extraretinal tissues. To test the possibility that UV-signals mediated by Opn5 would have a direct effect on the outer connective tissues of the eye, we first examined the expression patterns of a mammalian type Opn5 (Opn5m) in the late-embryonic chicken eye. Quantitative PCR showed Opn5m mRNA expression in the cornea and sclera. The anti-Opn5m antibody stained a small subset of cells in the corneal stroma and fibrous sclera. We next assessed the effect of UV-A (375 nm) irradiation on the chicken fibroblast cell line DF-1 overexpressing chicken Opn5m. UV-A irradiation for 30 min significantly increased the expression of Early growth response 1 (Egr1), known as an immediate early responsive gene, and of Matrix metalloproteinase 2 (Mmp2) in the presence of retinal chromophore 11-cis-retinal. In contrast, expression of Transforming growth factor beta 2 and Tissue inhibitor of metalloproteinase 2 was not significantly altered. These results indicate that UV-A absorption by Opn5m can upregulate the expression levels of Egr1 and Mmp2 in non-neuronal, fibroblasts. Taken together with the presence of Opn5m in the cornea and sclera, it is suggested that UV-A signaling mediated by Opn5 in the extraretinal ocular tissues could influence directly the outer connective tissues of the chicken late-embryonic eye.
AB - Recent studies show that exposure to ultraviolet (UV) light suppresses ocular elongation, which causes myopia development. However, the specific mechanisms of this process have not been elucidated. A UV-sensor, Opsin 5 (Opn5) mRNA was shown to be present in extraretinal tissues. To test the possibility that UV-signals mediated by Opn5 would have a direct effect on the outer connective tissues of the eye, we first examined the expression patterns of a mammalian type Opn5 (Opn5m) in the late-embryonic chicken eye. Quantitative PCR showed Opn5m mRNA expression in the cornea and sclera. The anti-Opn5m antibody stained a small subset of cells in the corneal stroma and fibrous sclera. We next assessed the effect of UV-A (375 nm) irradiation on the chicken fibroblast cell line DF-1 overexpressing chicken Opn5m. UV-A irradiation for 30 min significantly increased the expression of Early growth response 1 (Egr1), known as an immediate early responsive gene, and of Matrix metalloproteinase 2 (Mmp2) in the presence of retinal chromophore 11-cis-retinal. In contrast, expression of Transforming growth factor beta 2 and Tissue inhibitor of metalloproteinase 2 was not significantly altered. These results indicate that UV-A absorption by Opn5m can upregulate the expression levels of Egr1 and Mmp2 in non-neuronal, fibroblasts. Taken together with the presence of Opn5m in the cornea and sclera, it is suggested that UV-A signaling mediated by Opn5 in the extraretinal ocular tissues could influence directly the outer connective tissues of the chicken late-embryonic eye.
KW - Chicken
KW - Egr1
KW - Fibroblasts
KW - Mmp2
KW - Opsin 5
KW - UV-Absorbing pigment
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U2 - 10.1016/j.bbrep.2019.100665
DO - 10.1016/j.bbrep.2019.100665
M3 - Article
AN - SCOPUS:85069626794
SN - 2405-5808
VL - 19
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
M1 - 100665
ER -