Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus

Abstract

Recent studies have demonstrated the defocus sign-dependent, bidirectional gene expression regulation of bone morphogenetic proteins, BMP2, 4 and 7 in chick RPE. In this study, we examined the effects of imposed positive (+10 D) and negative (-10 D) lenses on the gene expression of these BMPs and BMP receptors (BMPR1A, BMPR1B, BMPR2) in chick retina and choroid after monocular lens treatment for 2 or 48 h, as indicators of the roles of retinal and choroidal BMPs and receptors in postnatal eye growth regulation. In retina, although all genes were expressed, neither +10 nor -10 D lenses, worn for either 2 or 48 h, significantly altered gene expression. In contrast, treatment-related differential gene expression was detected in the choroid for both BMPs and their receptors, although interestingly, with the +10 D lens, BMP2 was up-regulated by 156.7 ± 19.7% after 2 h, while BMPR1A was down-regulated to 82.3 ± 12.5% only after 48 h. With the -10 D lens, only the gene expression of BMPR1B was significantly altered, being up-regulated by 162.3 ± 21.2% after 48 h. Untreated birds showed no difference in expression between their two eyes, for any of the genes examined. The finding that retinal gene expression for BMP2, 4, 7 and their receptors are not affected by short-term optical defocus contrasts with previous observations of sign-dependent expression changes for the same genes in the RPE. The latter changes were also larger and more consistent in direction than the choroidal gene expression changes reported here. The interrelationship between these various changes and their biological significance for eye growth regulation are yet to be elucidated.

Keywords: Bone morphogenetic protein; Choroid; Myopia; Retina.

Figure 1

Interocular difference of refractive errors, normalized to baseline values, of eyes treated with +10 or −10 D lenses plotted as a function of treatment duration (2 or 48 h), as well as of fellow eyes of same birds and eyes of untreated chicks over same time frame. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 2

Interocular differences, normalized to baseline values, in axial length (AL), vitreous chamber depth (VCD), choroidal thickness (CT), and retinal thickness (RT) induced by monocular (A) +10 D and (B) −10 D lens treatments after for 2 and 48 h. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 3

mRNA levels of BMP2 (A), BMP4 (B), BMP7 (C), BMPR1A (D), BMPR1B (E), and BMPR2 (F) in retina after monocular +10 or −10 D treatment applied for 2 or 48 h. Comparison made between treated (dark bars) vs. fellow control (light bars) eyes of treated birds or right (dark bars) vs. left (light bars) eyes of untreated birds. None of the genes showed significant treatment-induced differential expression. Note differences in Y-axis scales for individual panels, used to offset gene-dependent differences in expression level.

Figure 4

Lens treatment-induced changes of retinal mRNA levels for BMP2, BMP4, BMP7, BMPR1A, BMPR1B, and BMPR2. Data are expressed as percentages (treated/fellow control eyes for lens treated birds and right/left eyes for untreated birds). None of the changes reached statistical significance.

Figure 5

mRNA levels of BMP2 (A), BMP4 (B), BMP7 (C), BMPR1A (D), BMPR1B (E), and BMPR2 (F) in choroid after +10 or −10 D lens treatment for 2 or 48 h. Comparison is made between treated vs. contralateral control eyes of monocularly treated birds or right vs. left eyes of untreated birds. Note differences in Y-axis scales for individual panels, used to offset gene-dependent differences in expression level. BMP2, BMPR1A, and BMPR1B all showed significant treatment-induced differential gene expression.* p < 0.05; ** p < 0.01.

Figure 6

Lens treatment-induced gene expression changes in choroid for BMP2, BMP4, BMP7, BMPR1A, BMPR1B, and BMPR2. Data are expressed as percentages (treated/fellow control eyes or right/left eyes). BMP2, BMPR1A, and BMPR1B all showed significant treatment-induced differential gene expression.