PT  - JOURNAL ARTICLE
AU  - Yalong Dang
AU  - Susannah Waxman
AU  - Chao Wang
AU  - Ralista T. Loewen
AU  - Ming Sun
AU  - Nils A. Loewen
TI  - Trabecular meshwork failure in a model of pigmentary glaucoma
AID  - 10.1101/118448
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 118448
4099  - http://biorxiv.org/content/early/2017/03/22/118448.short
4100  - http://biorxiv.org/content/early/2017/03/22/118448.full
AB  - Pigment dispersion syndrome can lead to pigmentary glaucoma (PG), a poorly understood condition of younger, myopic eyes with fluctuating, high intraocular pressure (IOP). The absence of a model similar in size and behavior to human eyes has made it difficult to investigate its pathogenesis. Here, we present a porcine ex vivo model that recreates the features of PG including intraocular hypertension, pigment accumulation in the trabecular meshwork and failure of phagocytosis. In in vitro monolayer cultures as well as in ex vivo eye perfusion cultures, we found that the cells that regulate outflow, the trabecular meshwork (TM) cells, form actin stress fibers, have a decreased phagocytosis and increased migration. Gene expression microarray and pathway analysis indicated key roles of RhoA and tight junctions in regulating the TM cytoskeleton, motility, and phagocytosis thereby providing new targets for PG therapy.