title: Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.
abstract: OBJECTIVE
  Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ.
  
  
  METHODS
  Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 μM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release.
  
  
  RESULTS
  Brimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells.
  
  
  CONCLUSIONS
  HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ramírez
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Javier
authors.initials: J
authors.lastname: Cáceres-del-Carpio
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Justin
authors.initials: J
authors.lastname: Chu
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chu
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.|2 Ophthalmology Department, Minia University , Minia, Egypt .
authors.forename: M Tarek
authors.initials: MT
authors.lastname: Moustafa
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Chwa
authors.affiliation: 3 Division of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology , London, United Kingdom .
authors.forename: G Astrid
authors.initials: GA
authors.lastname: Limb
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
authors.affiliation: 1 Gavin Herbert Eye Institute, University of California , Irvine, Irvine, California.|4 Department of Pathology and Laboratory Medicine, University of California Irvine , Irvine, California.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000068438:Brimonidine Tartrate / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D063928:Ependymoglial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology*
chemical_list: D000959:Antihypertensive Agents; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D000068438:Brimonidine Tartrate; D007770:L-Lactate Dehydrogenase