Abstract
Steroid-induced glaucoma is a severe pathological condition, sustained by a rapidly progressive increase in intraocular pressure (IOP), which is diagnosed in a subset of subjects who adhere to a glucocorticoid (GC)-based therapy. Molecular and clinical studies suggest that either natural or synthetic GCs induce a severe metabolic dysregulation of Trabecular Meshwork Cells (TMCs), an endothelial-derived histotype with phagocytic and secretive functions which lay at the iridocorneal angle in the anterior segment of the eye. Since TMCs physiologically regulate the composition and architecture of trabecular meshwork (TM), which is the main outflow pathway of aqueous humor, a fluid which shapes the eye globe and nourishes the lining cell types, GCs are supposed to trigger a pathological remodeling of the TM, inducing an IOP increase and retina mechanical compression. The metabolic dysregulation of TMCs induced by GCs exposure has never been characterized at the molecular detail. Herein, we report that, upon dexamethasone exposure, a TMCs strain develops a marked inhibition of the autophagosome biogenesis pathway through an enhanced turnover of two members of the Ulk-1 complex, the main platform for autophagy induction, through the Ubiquitin Proteasome System (UPS).
Highlights
The term glaucoma identifies a heterogeneous group of neurodegenerative disorders characterized by a loss of retinal ganglion cells (RGCs), degeneration of the optic nerve and irreversible blindness [1,2,3].Glaucoma is a multifactorial disease whose prevalent clinical presentation is represented by primary open-angle glaucoma (POAG), generally correlated with ageing, chronic redox imbalance and increased ocular pressure (IOP) [4,5,6].intraocular pressure (IOP) increase is supposed to be caused by the impaired drainage of the aqueous humor, a fluid which shapes and nourishes the tissue of the anterior segment of the eye through anatomical outflow pathways
A progressive IOP increase is observed in steroid-induced glaucoma, a severe clinical form of the disease, which is diagnosed in a subset of subjects who adhere to glucocorticoids (GC) therapy [10,11,12]
This research tool mirrors the existence of a severe acute clinical form of glaucoma, sustained by a progressive and relevant IOP increase, diagnosed in a subset of subjects who adhere to a GCs-based therapy for pre-existing pathologies [2,3,11,12]
Summary
Glaucoma is a multifactorial disease whose prevalent clinical presentation is represented by primary open-angle glaucoma (POAG), generally correlated with ageing, chronic redox imbalance and increased ocular pressure (IOP) [4,5,6]. IOP increase is supposed to be caused by the impaired drainage of the aqueous humor, a fluid which shapes and nourishes the tissue of the anterior segment of the eye through anatomical outflow pathways. The main outflow pathway is the trabecular meshwork (TM), a specialized tissue located at the iridocorneal angle through which the aqueous humor is drained into episcleral veins [3,7]. A progressive IOP increase is observed in steroid-induced glaucoma, a severe clinical form of the disease, which is diagnosed in a subset of subjects who adhere to glucocorticoids (GC) therapy [10,11,12].
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