Publication Date

2017-05-05

Availability

Embargoed

Embargo Period

2019-05-05

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2017-04-19

First Committee Member

Sanjoy K. Bhattacharya

Second Committee Member

Ralf Landgraf

Third Committee Member

Antonio Barrientos

Fourth Committee Member

Iok-Hou Pang

Abstract

Glaucoma refers to a group of late onset, except for juvenile open-angle glaucoma (JOAG), irreversible blinding diseases that are frequently associated with elevated intraocular pressure (IOP) and affects about 60.5 million people worldwide. The elevation of IOP in primary open angle glaucoma (POAG) occurs due to impeded aqueous humor (AH) outflow. There are two routes of AH outflow: conventional through trabecular meshwork (TM) and uveoscleral. The outflow is reduced in glaucoma due to increased resistance to outflow at TM. Lowering IOP is the only proven strategy for protecting the optic nerve from glaucomatous optic neuropathy even in a group of glaucoma patients in whom the IOP remains within normal range (termed normal tension glaucoma). Prostanoid lipids, members of eicosanoid subclass, were discovered in the iris in 1955, which were subsequently found to reduce IOP but various adverse side effects. Prostanoids are currently the most effective glaucoma medication. They reduce IOP by increasing AH outflow mainly via uveoscleral route and very little via conventional route. The role of different classes of endogenous lipids other than eicosanoids in glaucoma has not been investigated in a comprehensive manner. Our central hypothesis is that the endogenous lipids in the AH exist in the form of lipid vesicles; affects TM cell behavior, TM material properties and magnitude of IOP (IOP homeostasis). We also hypothesize that alteration of lipids in pathologic state (POAG) is likely contributed by changes in lipid metabolizing enzymes.

Keywords

Aqueous humor; Intraocular pressure; Primary open angle glaucoma; Phospholipids; Trabecular meshwork

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