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Nanomaterials and Retinal Toxicity
Boyes, W. Nanomaterials and Retinal Toxicity. Society of Toxicology Annual Meeting, New Orleans, LA, March 13 - 17, 2016.
This abstract will be presented at the Society of Toxicology Annual Meeting March 13-17, 2016, New Orleans, LA
The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature and then crossing the blood-retinal barrier; and through the choroidal blood supply, crossing the Bruch's membrane and the retinal pigment epithelium (RPE). The blood-retinal barrier is functionally similar to the blood-brain barrier, normally restricting transport of larger sized materials, but particles in the lower nanomaterial size range can be expected to transit. The blood flow to the retinal choroid is, on a tissue mass basis, one of the highest in the body raising the potential for rapid delivery of nanomaterials to the RPE. In vitro, RPE cells rapidly uptake nano particles, transport and agglomerate them in the perinuclear cytoplasm. In vivo studies have shown that the eye can uptake nanomaterials and retain them longer than many other tissues after cessation of exposure. Toxicity from nanomaterials to the neural retina or the RPE would be expected to follow common mechanisms identified for other tissues including generation of reactive oxygen species, alteration of cellular redox status, altered intracellular signaling, and release of toxic metal ions from soluble metallic particles. The retina and other ocular tissues, however, have potential for additional phototoxic mechanisms not relevant in other neural tissues due to the concurrent exposure to light. Titanium dioxide (Ti02) nanoparticles can be efficient photo catalysts generating superoxide and hydroxide radicals in aqueous media under UV wavelengths of exposure resulting in phototoxic damage to surrounding tissues. For potential drug development , fullerene and related materials, including the hydroxylated derivative, fullerol, which have been proposed for applications as drug carriers, show phototoxicity under both UVA and visible wavelengths. The potential for retinal toxicity including phototoxicity of nanomaterial-enabled ocular drug preparations may be important to consider as a component of drug development and safety evaluations.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION