Control of organ size has fascinated developmental biologists for many years. In the eye, changes in size and dimension can dramatically affect visual acuity, but the molecular mechanism controlling eye size is not fully understood. Now, Wenjun Xiong and colleagues identify a role for the transcription factor SREBP2 in controlling eye size by transcriptional repression of Lrp2, a low-density lipoprotein receptor family member, and Bmp2, a ligand in the BMP signalling pathway. They find that mice overexpressing Srebp2 in the retinal pigment epithelia, have enlarged eye globes. They correlate overexpression of Srebp2 with reduced mRNA levels of Lrp2, a known regulator of eye overgrowth, and confirm that SREBP2 is a transcriptional repressor of Lrp2. Using RNA-sequencing data, they detect downregulation of target genes from the BMP signalling pathway in mice with enlarged eyes. They discover that Bmp2 is transcriptionally repressed by SREBP2 but activated by LRP2, and depletion of Bmp2 causes eye overgrowth whereas overexpression of Bmp2 leads to smaller eyes. Finally, they show that eye overgrowth phenotypes linked to high myopia, caused by mutation of Lrp2, can be rescued by overexpression of Bmp2. Together, these data identify a new signalling pathway responsible for controlling eye size and may have important implications for the treatment of myopia.
