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).

Sbardella, D., Tundo, G.r., Coletta, M., Manni, G., Oddone, F. (2021). Dexamethasone downregulates autophagy through accelerated turn-over of the ulk-1 complex in a trabecular meshwork cells strain: Insights on steroid-induced glaucoma pathogenesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(11), 5891 [10.3390/ijms22115891].

Dexamethasone downregulates autophagy through accelerated turn-over of the ulk-1 complex in a trabecular meshwork cells strain: Insights on steroid-induced glaucoma pathogenesis

Tundo G. R.;Coletta M.;Manni G.;
2021-01-01

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).
2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
autophagy
glaucoma
glucocorticoids
intraocular pressure
trabecular meshwork
ubiquitin proteasome system
Apoptosis
Autophagy
Autophagy-Related Protein-1 Homolog
Cell Proliferation
Dexamethasone
Disease Susceptibility
Glaucoma
Humans
Intracellular Signaling Peptides and Proteins
Multiprotein Complexes
Proteasome Endopeptidase Complex
Trabecular Meshwork
Sbardella, D., Tundo, G.r., Coletta, M., Manni, G., Oddone, F. (2021). Dexamethasone downregulates autophagy through accelerated turn-over of the ulk-1 complex in a trabecular meshwork cells strain: Insights on steroid-induced glaucoma pathogenesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(11), 5891 [10.3390/ijms22115891].
Sbardella, D; Tundo, Gr; Coletta, M; Manni, G; Oddone, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/279154
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