Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells

Significance The trabecular meshwork is the major tissue regulating intraocular pressure (IOP). Malfunction of this tissue results in ocular hypertension, the major risk factor for glaucoma. How IOP is regulated is still unknown, but it is accepted that mechanosensation and mechanotransduction are critical regulators. In this study, we report that primary cilia (PC) is a mechanosensor for stretch-induced autophagy in TM cells and identified a reciprocal activation of AKT1 and SMAD2/3 as a signaling pathway regulating the activation of autophagy by PC. Most importantly, we showed that PC-mediated autophagy plays a critical role in IOP homeostasis. These findings tremendously contribute to our understanding of TM biology and identify new potential targets for therapeutic strategies.