Proteomics of pseudoexfoliation materials in the anterior eye segment

Abstract

Pseudoexfoliation syndrome (PEX) is characterized by the production of white extracellular fluffy clumps of microfibrillar material that aggregates in various organs throughout the body but is known to cause disease in the eye. The accumulation of PEX material (PEXM) in the anterior segment ocular structures is believed to cause an increase in intraocular pressure (IOP) resulting in pseudoexfoliation glaucoma (PEXG). The onset of PEXG is often bilateral but asymmetric-one eye often presents with glaucoma prior to the other eye. Proteomics has been used to identify key proteins involved in PEXM formation with the end goal of developing effective treatments for PEX and PEXG which may act through inhibiting the formation of the PEX aggregates. To date, a variety of proteins with various molecular functions have been identified from extracted anterior segment structures and fluids, such as aqueous humor (AH) and blood serum of patients affected by PEX. From past studies, some proteins identified in AH, lens capsule epithelium, iris tissue, and blood serum samples include vitamin D binding protein (GC), apolipoprotein A4 (APOA4), lysyl oxidase like-1 (LOXL1), complement C3, beta-crystalline B1, and B2, and antithrombin-III (SERPINC1). Each of these proteins have been observed in eyes with PEX at varying levels within the different eye structures. In this review, we further examine the anterior segment ocular proteomics of PEXM from past studies to better understand the mechanism of PEX and PEXG development. Both genetic and environmental risk factors have been implicated to be involved in the development of PEX and PEXG. This field is at an early stage of investigation identifying how these factors modify proteins both at the expression and functional level to cause changes leading to the pathophysiology of PEX glaucoma.

Keywords: Anterior eye segment; Aqueous humor; Glaucoma; Proteins; Proteomics; Pseudoexfoliation; Pseudoexfoliation glaucoma; Pseudoexfoliation material; Pseudoexfoliation syndrome.