PPARγ modulates refractive development and form deprivation myopia in Guinea pigs

Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferatoractivated receptor gamma (PPAR gamma) expression modulate hypoxia-induced pathological responses. We determined if PPAR gamma modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1 alpha) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPAR gamma antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1 alpha and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1 alpha expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1 alpha upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPAR gamma modulates collagen expression levels and FDM through an inverse relationship between changes in PPAR gamma and HIF-1 alpha expression levels.

Automated summary

PPAR gamma modulates the progression of form deprivation myopia by influencing choroidal thickness, choroidal blood perfusion, and scleral hypoxia-inducible transcription factor, which in turn regulate scleral collagen type 1 expression levels.