Effects of imposed defocus of opposite sign on temporal gene expression patterns of BMP4 and BMP7 in chick RPE

This study investigated the effects of imposed optical defocus on the expression patterns of bone morphogenetic protein 4 and 7 (BMP4, BMP7) in chick retinal pigment epithelium (RPE), as indicators of roles in postnatal eye growth regulation. BMP4 and BMP7 gene and protein expression patterns were characterized for retina, RPE and choroid tissues of young normal White-Leghorn chickens. The effects of short-term (2 and 48 h) exposure to monocular +10 and −10 diopter (D) lenses on RPE gene expression of BMP4 and BMP7 were also examined. Tissues from both treated and fellow eyes as well as from eyes of age-matched untreated birds were included in the latter experiment. Of ocular tissues comprising the posterior wall of the chick eye, RPE showed the highest expression of BMP4 and BMP7 mRNA, compared to retina and choroid. Western blots and immunohistochemistry confirmed the expression of BMP4 and BMP7 protein in all layers – retina, RPE, choroid and sclera. With imposed defocus, both BMP4 and BMP7 showed bidirectional changes in expression in RPE, however, with different temporal patterns. With +10 D lenses, BMP4 gene expression was up-regulated after both 2 and 48 h of treatment, while BMP7 expression was up-regulated only after 48 h of lens wear. With −10 D lenses, both BMP4 and BMP7 showed down-regulation of gene expression for both 2 and 48 h treatment durations. With the −10 D lens treatment applied for 48 h, gene expression for both BMP4 and BMP7 was also down-regulated in contralateral fellows of treated eyes compared to eyes of untreated chicks. The rapid changes in gene expression in chick RPE observed for both BMP4 and BMP7, up or down according to the sign of imposed optical defocus, resemble similar trends reported for BMP2. Further studies are needed to confirm the roles of BMPs as ocular growth modulators, as suggested by these data. The data also suggest a role for the RPE as a conduit for relaying growth modulatory retinal signals.

► BMP4 and -7 are widely expressed in the posterior ocular tissues of young chicks. ► RPE shows high BMP4 and -7 gene expression compared to retina and choroid. ► BMP4 and -7 gene expression in RPE is sensitive to the sign of optical defocus. ► RPE acts as a conduit for retinal growth signals targeting the choroid and sclera. ► BMP4 and BMP7 are plausible ocular growth modulators in the chick eye.