Lifetime exposure of ambient PM2.5 elevates intraocular pressure in young mice.

Abstract Epidemiological studies suggest that ambient particulate matter exposure may be a new risk factor of glaucoma, but it lacks solid experimental evidence to establish a causal relationship. In this study, young mice (4 weeks old) were exposed concentrated ambient PM2.5 (CAP) for 9 months, which is throughout most of the life span of a mouse under heavy pollution. CAP was introduced using a versatile aerosol concentration enrichment system which mimics natural PM2.5 exposure. CAP exposure caused a gradual elevation of intraocular pressure (IOP) and an increase in aqueous humor outflow resistance. In the conventional outflow tissues that regulates IOP, inducible nitric oxide synthase (iNOS) was up-regulated and 3-nitrotyrosine (3-NT) formation increased. At the cellular level, PM2.5 exposure increased the transendothelial electrical resistance of cells that control IOP (AAP cells). This is accompanied by increased reactive oxygen species (ROS), iNOS and 3-NT levels. Peroxynitrite scavenger MnTMPyP successfully treated the IOP elevation and restored it to normal levels by reducing 3-NT formation in outflow tissues. This study provides the novel evidence that in young mice, lifetime whole-body PM2.5 exposure has a direct toxic effect on intraocular tissues, which imposes a significant risk of IOP elevation and may initiate the development of ocular hypertension and glaucoma. This occurs as a result of protein nitration of conventional aqueous humor outflow tissues.