The molecular pathophysiology of pseudoexfoliation glaucoma

Abstract

This review summarizes recent observations and discoveries important for a current understanding of the clinical, molecular and genetic aspects of pseudoexfoliation glaucoma. Significant advances in our understanding of the molecular nature of the pseudoexfoliation material and pseudoexfoliation glaucoma have recently been made in the transcriptome, proteome, and genome levels. Differential gene expression studies have identified gene transcripts that are significantly downregulated and upregulated in the eyes of patients with pseudoexfoliation glaucoma relative to nonglaucomatous controls. Many of these differentially regulated genes are involved with extracellular matrix structure and metabolism and responses to stress and inflammation. Proteomic analysis of the pseudoexfoliation material similarly suggests that extracellular matrix and stress response proteins are associated with pseudoexfoliation glaucoma. Most recently, LOXL1 (which is involved with extracellular matrix formation and stability) has been discovered to be the first gene associated with a risk of developing pseudoexfoliation glaucoma. A proposed protein sink model parsimoniously accounts for the multitude of proteins known to be associated with pseudoexfoliation material and describes the orderly molecular formation of this disease causing material in the eye. Our understanding of pseudoexfoliation glaucoma has recently been significantly advanced by cutting edge molecular and genetic approaches to studying this sight threatening disease. An increased understanding of the molecular pathophysiology of pseudoexfoliation glaucoma will lead to improved management and diagnosis and new treatments for pseudoexfoliation glaucoma.