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1 General aspects (0)   1.1 Epidemiology (13)   1.2 Population genetics (0)   1.3 Pathogenesis (6)   1.4 Quality of life (7)   1.5 Glaucomas as cause of blindness (5)   1.6 Prevention and screening (6) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (6)   2.2 Cornea (17)   2.3 Sclera (14)   2.4 Anterior chamber angle (6)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (16)     2.5.2 Schlemms canal (4)     2.5.3 Scleral outlet channels (2)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (0)     2.6.2 Outflow (0)       2.6.2.1 Trabecular meshwork (1)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (1)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (6)   2.9 Ciliary body (1)   2.10 Lens (1)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (18)   2.13 Retina and retinal nerve fibre layer (33)   2.14 Optic disc (34)   2.15 Optic nerve (2)   2.16 Chiasma and retrochiasmal central nervous system (4)   2.17 Stem cells (5)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (5)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (4)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (2)     3.4.2 Gene studies (29)   3.5 Molecular biology incl. 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    12.8.1 Without tube implant (13)     12.8.2 With tube implant or other drainage devices (29)     12.8.3 Non-perforating (2)     12.8.4 Using laser (0)     12.8.5 Other (2)     12.8.10 Woundhealing antifibrosis (13)     12.8.11 Complications, endophthalmitis (10)   12.9 Trabeculotomy, goniotomy (10)   12.10 Cyclodestruction (3)   12.11 Cyclodialysis (1)   12.12 Cataract extraction (1)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (4)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (7)   12.15 Capsulotomy (0)   12.16 Vitrectomy (2)   12.17 Anesthesia (5)   12.20 Other (1) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (2)   13.2 Outcome (0)     13.2.1 IOP (2)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (4) 15 Miscellaneous (23)

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Abstract #69195 Published in IGR 18-1

Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53

Kalouche G; Boucher C; Coste A; Debussche L; Orsini C; Baudouin C; Debeir T; Vigé X; Rostène W
Biochimica et Biophysica Acta 2016; 1863: 2322-2332

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E-prostanoid receptor subtype 2 (EP2) agonists are currently under clinical development as hypotensive agents for the treatment of ocular hypertension. However, the effects of EP2 receptor agonists on trabecular meshwork (TM) alterations leading to primary open-angle glaucoma (POAG) are still unknown. Here, we evaluated whether EP2 receptor activation exhibits protective functions on TM cell death induced by endoplasmic reticulum (ER) stress. We show that the EP2 receptor agonist butaprost protects TM cell death mediated by the ER stress inducer tunicamycin through a cyclic AMP (cAMP)-dependent mechanism, but independent of the classical cAMP sensors, protein kinase A and exchange proteins activated by cAMP. The ER stress-induced intrinsic apoptosis inhibited by the EP2 receptor agonist was correlated with a decreased accumulation of the cellular stress sensor p53. In addition, p53 down-regulation was associated with inhibition of its transcriptional activity, which led to decreased expression of the pro-apoptotic p53-upregulated modulator of apoptosis (PUMA). The stabilization of p53 by nutlin-3a abolished butaprost-mediated cell death protection. In conclusion, we showed that EP2 receptor activation protects against ER stress-dependent mitochondrial apoptosis through down-regulation of p53. The specific inhibition of this pathway could reduce TM alterations observed in POAG patients.

Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France; Sanofi Research & Development, Translational Sciences Unit, Chilly-Mazarin 91380, France. Electronic address: georges.kalouche@sanofi.com.

Full article

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Classification:

2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
11.4 Prostaglandins (Part of: 11 Medical treatment)

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