TGF-ß induces phosphorylation of phosphatase and tensin homolog: implications for fibrosis of the trabecular meshwork tissue in glaucoma.

Fundamental cell signaling mechanisms that regulate dynamic remodeling of the extracellular matrix (ECM) in mechanically loaded tissues are not yet clearly understood. Trabecular meshwork (TM) tissue in the eye is under constant mechanical stress and continuous remodeling of ECM is crucial to maintain normal aqueous humor drainage and intraocular pressure (IOP). However, excessive ECM remodeling can cause fibrosis of the TM as in primary open-angle glaucoma (POAG) patients, and is characterized by increased resistance to aqueous humor drainage, elevated IOP, optic nerve degeneration and blindness. Increased levels of active transforming growth factor-ß2 (TGF-ß2) in the aqueous humor is the main cause of fibrosis of TM in POAG patients. Herein, we report a novel finding that, in TM cells, TGF-ß-induced increase in collagen expression is associated with phosphorylation of phosphatase and tensin homolog (PTEN) at residues Ser380/Thr382/383. Exogenous overexpression of a mutated form of PTEN with enhanced phosphatase activity prevented the TGF-ß-induced collagen expression by TM cells. We propose that rapid alteration of PTEN activity through changes in its phosphorylation status could uniquely regulate the continuous remodeling of ECM in the normal TM. Modulating PTEN activity may have high therapeutic potential to alleviating the fibrosis of TM in POAG patients.

Prospective evaluation of intraoperative intraocular lens stress fracture during cataract surgery.

PURPOSE: To determine the incidence and risk factors of intraocular lens (IOL) stress fracture during cataract surgery. SETTING: Ivey Eye Institute, London, Ontario, Canada. DESIGN: Prospective, randomized cohort study. METHODS: Patients scheduled for routine cataract surgery were randomized into 2 study groups. The 2 groups only differed in the use of Monarch IOL delivery cartridges for insertion of an Acrysof IQ SN60WF IOL. The cartridge C group used Monarch cartridge C, and the cartridge D group used Monarch cartridge D. Patients were examined for IOL stress fractures. RESULTS: A total of 386 study eyes were enrolled. The overall incidence of IOL stress fracture was 6.22%. The incidence of IOL stress fracture with cartridge C and cartridge D groups were 3.16% and 9.18%, respectively (P = .01). The IOL stress fracture rate for IOL power less than 18.0 D was 3.45%, IOL power between 18.0 D to 23.5 D was 6.49%, and IOL power over 23.5 D was 10.81%. A total of 24 IOL stress fractures were observed. Among IOL stress fractures, 45.8% were equal to or less than 1.0 mm in length. Two thirds of stress fractures were located over the central 4 mm of the IOL optic. No subjective adverse visual outcomes were reported from any of the observed IOL stress fractures. CONCLUSION: Intraocular lens stress fracture is recognizable risk during cataract surgery. Risk factors for IOL stress fracture include smaller IOL delivery cartridges and IOLs of higher refractive powers. There was a low risk for IOL stress fracture resulting in adverse subjective visual outcomes.