Retinal defocus and form‐deprivation induced regional differential gene expression of bone morphogenetic proteins in chick retinal pigment epithelium

Abstract

We previously reported bidirectional gene expression regulation of the Bone Morphogenetic Proteins (BMP2, 4, and 7) in chick retinal pigment epithelium (RPE) in response to imposed optical defocus and form-deprivation (FD). This study investigated whether there are local (regional) differences in these effects. 19-day old White-Leghorn chicks wore monocular +10 or − 10 D lenses, or diffusers (FD) for 2 or 48 hr, after which RPE samples were collected from both eyes, from a central circular zone (3 mm radius), and 3 mm wide annular mid-peripheral and peripheral zones in all cases. BMP2, 4, and 7 gene expression levels in RPE from treated and fellow control eyes were compared as well as differences across zones. With the +10 D lens, increased expression of both BMP2 and BMP4 genes was observed in central and mid-peripheral zones but not the peripheral zone after 2 and 48 hr. In contrast, with the −10 D lens BMP2 gene expression was significantly decreased in all three zones after 2 and 48 hr. Similar patterns of BMP2 gene expression were observed in all three zones after 48 hr of FD. Smaller changes were recorded for BMP4 and BMP7 gene expression for both myopia-inducing treatments. That optical defocus-and FD-induced changes in BMP gene expression in chick RPE show treatment-dependent local (regional) differences suggest important differences in the nature and contributions of local retinal and underlying RPE regions to eye growth regulation.

Gene Expression Signatures of Contact Lens-Induced Myopia in Guinea Pig Retinal Pigment Epithelium

“… 37 – 40 For example, Bmp2 gene expression was found to be downregulated in RPE in a chick model of lens-induced myopia. 14 , 16 , 41 The finding in the current study of significant downregulation of Bmp2 gene expression in RPE after just one day of −10 D CL wear is consistent with this finding in chicks. 14 , 16 , 41 BMP2 has also been reported to inhibit adult human RPE cell proliferation, 42 consistent with the profile of a negative growth regulator, although BMP2 is reported to stimulate the proliferation and differentiation of human scleral fibroblasts in vitro.…”

“… 14 , 16 , 41 The finding in the current study of significant downregulation of Bmp2 gene expression in RPE after just one day of −10 D CL wear is consistent with this finding in chicks. 14 , 16 , 41 BMP2 has also been reported to inhibit adult human RPE cell proliferation, 42 consistent with the profile of a negative growth regulator, although BMP2 is reported to stimulate the proliferation and differentiation of human scleral fibroblasts in vitro. 43 , 44 These opposing patterns of behavior may reflect differences in the roles of various ocular tissues in homeostasis and eye growth modulation.…”

Global Tendency and Frontiers of Research on Myopia From 1900 to 2020: A Bibliometrics Analysis

“…According to recent studies by Wildsoet CF, the Bone Morphogenetic Proteins (BMP 2, 4, and 7) gene is down-regulated with form-deprivation and hyperopic defocus, and up-regulated with myopic defocus in chicks, which exhibited regional differences in retinal pigment epithelium. Consequently, it is tempting to speculate that BMPs played a crucial role in ocular growth signaling ( 95 , 96 ).…”

RNA sequence analysis identified bone morphogenetic protein-2 (BMP2) as a biomarker underlying form deprivation myopia

“…Numerous mechanisms were detected to be associated with FDM through functional annotation of the DEGs. Among them, some have been reported to be related to myopia, including immunity [ 31 , 32 ], inflammation [ [32] , [33] , [34] ], and BMP2 upregulation [ 35 , 36 ]. We further analyzed the efficiency of BMP2 dysregulation on myopic retina by comparing early and late recovery from FDM.…”