Publication Date

2017-08-11

Availability

Open access

Embargo Period

2017-08-11

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2017-07-27

First Committee Member

Sanjoy K. Bhattacharya

Second Committee Member

Arun Malhotra

Third Committee Member

Ibolya Edit Andras

Fourth Committee Member

Amjad Farooq

Fifth Committee Member

Carol B. Toris

Abstract

Glaucoma affects over 70 million people worldwide and can result in irreversible progressive vision loss if left untreated. Primary open angle glaucoma is the most common form of the disease. This disease is characterized by an uncontrolled increase in intraocular pressure (IOP) and this characteristic remains the only modifiable risk factor. The trabecular meshwork (TM) is a filter-like structure responsible for aqueous humor filtration into Schlemm’s canal (SC) and into the episcleral veins (EV). It is believed that obstruction in the TM leads to impeded aqueous humor outflow resulting in an increase in IOP. It has previously been demonstrated that the extracellular matrix protein cochlin forms deposits in the TM of glaucomatous individuals compared to controls and may contribute to impeded aqueous humor outflow. Our group has shown how TM cells detect shear stress via the interaction of cochlin with the cell surface bound, stretch-activated channel TREK-1. Uncontrolled increase in resistance, a mechanism that typically contributes to the segmental outflow pattern in a regulated manner in the eye, is also thought to be a contributing factor to the increase in IOP. In this study, we characterize segmental outflow in the DBA/2J and DBA/2J-Gpnmb+/SjJ mouse model and further investigate the role the extracellular matrix protein cochlin plays in mechanotransduction of TM cells for IOP regulation.

Keywords

Glaucoma; Intraocular pressure; Aqueous humor outflow; Trabecular meshwork; Extracellular matrix; Mechanotransduction

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