Purchase this article with an account.
Anna K. Junk, Sarah R. Wellik, Sanjoy K. Bhattacharya; Accumulation of Proteasomal Aggregates and Reduced Proteolytic Activities and in the Trabecular Meshwork in Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1510.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate proteolytic activities in the trabecular meshwork of patients with primary open angle glaucoma (POAG).
Trabecular meshwork (TM) specimen from 15 patients with POAG were collected during trabeculectomy surgery and flash frozen at -80º C. Control TM tissue was obtained from the scleral rim of corneal transplant donors. The 15 donors were age and gender matched but not affected with glaucoma. Proteins were isolated using established procedures and subjected to Western Blot analysis, mass spectrometry and enzymatic activity assays. This research was conducted following the tenets of the declaration of Helsinki.
Glaucomatous TM revealed notably increased amounts of proteasomal aggregates compared to controls. Both, calpain-1 and cathepsin D immunoreactivity levels were elevated in glaucomatous TM. However, the enzymatic activities of both calpain-1 and cathepsin D were reduced in the glaucomatous TM compared to controls.
Recent literature supports a role of oxidative protein damage in the etiology of POAG. Modified, inactive calpain-1 protease may accumulate in the trabecular meshwork of patients with glaucoma. Reduced enzymatic activity of both calpain-1 and the lysosomal protease cathepsin D may be involved in the pathophysiology of POAG, contributing to the accumulation of proteasomal aggregates and thereby affecting TM outflow resistance. These data suggest that reduced proteolytic activities of calpain-1 and cathepsin D in the TM contribute to the pathophysiology of POAG.
This PDF is available to Subscribers Only