title: Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration.
abstract: Photoreceptor (PR) cells are prone to accumulation of reactive oxygen species (ROS) and oxidative stress. An imbalance between the production of ROS and cellular antioxidant defenses contributes to PR degeneration and blindness in many different ocular disease states. Yttrium oxide (Y2O3) nanoparticles (NPs) are excellent free radical scavengers owing to their nonstoichiometric crystal defects. Here we utilize a murine light-stress model to test the efficacy of Y2O3 NPs (~10-14nm in diameter) in ameliorating retinal oxidative stress-associated degeneration. Our studies demonstrate that intravitreal injections of these NPs at doses ranging from 0.1 to 5.0µM 2 weeks before acute light stress protect PRs from degeneration. This protection is reflected both structurally (i.e., decreased light-associated thinning of the outer nuclear layer) and functionally (i.e., preservation of scotopic and photopic electroretinogram amplitudes). We also observe preservation of structure and function when NPs are delivered immediately after acute light stress, although the magnitude of the preservation is smaller, and only doses ranging from 1.0 to 5.0µM were effective. We show that the Y2O3 NPs are nontoxic and well tolerated after intravitreal delivery. Our results suggest that Y2O3 NPs have astonishing antioxidant benefits and, with further exploration, may be an excellent strategy for the treatment of oxidative stress associated with multiple forms of retinal degeneration.
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Rajendra N
authors: RN
authors: Mitra
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Miles J
authors: MJ
authors: Merwin
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Zongchao
authors: Z
authors: Han
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Shannon M
authors: SM
authors: Conley
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Muayyad R
authors: MR
authors: Al-Ubaidi
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: muna-naash@ouhsc.edu.
authors: Muna I
authors: MI
authors: Naash
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000494:pharmacology*; D058449:Intravitreal Injections; D008027:Light / Q000009:adverse effects; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012162:Retinal Degeneration / Q000517:prevention & control*; D015019:Yttrium / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D015019:Yttrium; C091417:yttria
keywords: Free radicals; Light damage; Nanoparticle; Oxidative stress; Photoreceptors; Rescue; Y(2)O(3)