Herbert Wertheim School Optometry and Vision Science, University of California, Berkeley, California, United States of America.
Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2024 Oct 11;19(10):e0311505. doi: 10.1371/journal.pone.0311505. eCollection 2024.
This study investigated the differential gene expression of BMPs in chick retinal pigment epithelium (RPE) during recovery from short term exposure to optical defocus and form-deprivation (FD) treatments.
14-day old White-Leghorn chicks wore either monocular +10 or -10 D lenses, or diffusers for 2 or 48 h, after which eyes were allowed unobstructed vision for up to 96 h. Over this recovery period, refractive errors and choroidal thickness (ChT) were tracked using retinoscopy and high-frequency A-scan ultrasonography. Real-time PCR was used to examine the expression of BMP2, 4, and 7 genes in RPE samples collected 0, 15 min, 2, 24, 48, and 96 h after the termination of treatments. Expression levels in treated eyes and their contralateral control eyes were compared.
After the termination of the lens and diffuser treatments, eyes gradually recovered from induced shifts in refractive error. With all three treatments, ChT changes reached statistical significance after 48 h of treatment, be it thinning with the -10 D lens and diffuser treatments (-0.06 ± 0.03mm, p < 0.05; -0.11 ± 0.04 mm, p < 0.05, resp.), or thickening with the +10 D lens (0.31 ± 0.04 mm, p < 0.001). BMP2 gene expression was rapidly upregulated in eyes wearing the +10 D lens, being statistical significance after 2 h, as well as 48 h of treatment. With the 2 h treatment, the latter gene expression pattern persisted for 15 min into the recovery period, before decreasing to the same level as that of contralateral control eyes, with a short-lived rebound, i.e., upregulation, 24 h into the recovery period. With the longer, 48 h treatment, BMP2 gene expression decreased more gradually, from 739 ± 121% at the end of the treatment period, to 72 ± 14% after 48 h of recovery. Two and 48 h of both -10 D and FD treatments resulted in BMP2 gene expression downregulation, with the time taken for gene expression levels to fully recover varying with the duration of initial treatments. In both cases, BMP2 gene expression downregulation persisted for 15 min into the recovery period, but reversed to upregulation by 2 h. Similar gene expression patterns were also observed for BMP4, although the changes were smaller.
The observed changes in BMP gene expression in chick RPE imply dynamic, albeit complex regulation, with the duration of exposure and recovery being critical variables for all three types of visual manipulations. This study provides further evidence for a role of the RPE as an important signal relay linking the retina to the choroid and sclera in eye growth regulation.
本研究旨在探讨鸡视网膜色素上皮（RPE）中 BMPs 在短期光学离焦和形觉剥夺（FD）处理后恢复过程中的差异基因表达。
14 日龄白来航鸡佩戴单眼+10 或-10 D 透镜或扩散器 2 或 48 h，然后允许眼睛不受阻碍地恢复长达 96 h。在此恢复期间，使用视网膜检影术和高频 A 型超声扫描跟踪屈光不正和脉络膜厚度（ChT）的变化。在处理结束后 0、15 min、2、24、48 和 96 h 采集 RPE 样本，使用实时 PCR 检测 BMP2、4 和 7 基因的表达。比较处理眼及其对侧对照眼的表达水平。
在终止透镜和扩散器处理后，眼睛逐渐从诱导的屈光误差中恢复。对于所有三种处理方式，在 48 h 的处理后，ChT 变化均达到统计学意义，无论是 -10 D 透镜和扩散器处理引起的变薄（-0.06 ± 0.03mm，p < 0.05；-0.11 ± 0.04mm，p < 0.05），还是+10 D 透镜处理引起的增厚（0.31 ± 0.04mm，p < 0.001）。佩戴+10 D 透镜的眼睛中 BMP2 基因表达迅速上调，在 2 h 时以及 48 h 的处理时具有统计学意义。对于 2 h 的处理，后者的基因表达模式在恢复期间持续 15 min，然后在恢复期间的 24 h 内降低到与对侧对照眼相同的水平，出现短暂的反弹，即上调。对于较长的 48 h 处理，BMP2 基因表达的下降更为缓慢，从处理期末的 739 ± 121%下降到 48 h 恢复后的 72 ± 14%。两种 -10 D 和 FD 处理持续 2 和 48 h 导致 BMP2 基因表达下调，基因表达水平完全恢复所需的时间随初始处理时间的长短而变化。在这两种情况下，BMP2 基因表达的下调在恢复期间持续 15 min，但在 2 h 时恢复为上调。BMP4 也观察到类似的基因表达模式，尽管变化较小。
鸡 RPE 中 BMP 基因表达的变化表明存在动态但复杂的调控，暴露和恢复的持续时间是所有三种类型的视觉处理的关键变量。本研究进一步证明了 RPE 作为连接视网膜与脉络膜和巩膜的重要信号中继的作用，在眼生长调节中发挥作用。
