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Bidirectional, optical sign-dependent regulation of BMP2 gene expression in chick retinal pigment epithelium
Yan Zhang1, Yue Liu, Christine F Wildsoet
1Center for Eye Disease & Development, Vision Science Program & School of Optometry, University of California, Berkeley, Berkeley, California 94720, USA. yanzhang@berkeley.edu
Purpose:
We explored the role of bone morphogenic protein 2 (BMP2) in defocus-induced ocular growth using gene expression changes in RPE as a surrogate.
Methods:
Young White-Leghorn chickens were used in this study. Normal gene expression of BMP2 and its receptors was examined in retina, RPE, and choroid, and BMP2 protein expression assessed in the same tissues using Western blots and immunohistochemistry. Quantitative PCR (qPCR) was used to assess the effects of short-term exposure (2 or 48 hours) to monocular +10 and -10 diopter (D) lenses, on RPE gene expression of BMP2 and its receptors. Ocular growth was assessed using A-scan ultrasonography.
Results:
In the eyes of untreated chickens, BMP2 mRNA was expressed more highly in RPE compared to retina and choroid and all three tissues expressed BMP2 protein. The gene expression for all three receptors also was detected in these tissues, with BMPR2 showing highest and BMPR1B lowest expression. BMP2 was up-regulated in the RPE from eyes wearing +10 D lenses, which exhibited shorter than normal vitreous chambers (VCDs) and thickened choroids, while BMP2 was down-regulated in the RPE from eyes wearing -10 D lenses, which developed enlarged VCDs. These treatments did not induce differential expression of BMP receptors in RPE.
Conclusions:
That mRNA expression of BMP2 in chick RPE shows bidirectional, defocus sign-dependent changes is suggestive of a role for BMP2 in eye growth regulation, although the diffuse ocular expression of BMP2 and its receptors suggests complex growth-modulatory signal pathways.
