title: Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after experimental retinal detachment.
abstract: BACKGROUND
  Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents.
  
  
  RESULTS
  Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651±68/mm(2) vs. 1314±68/mm(2), P = 0.001) and prevented the reduction of ONL thickness ratio (0.84±0.03 vs. 0.65±0.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment.
  
  
  CONCLUSIONS
  Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.
authors.affiliation: Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Mantopoulos
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Jason
authors.initials: J
authors.lastname: Comander
authors.forename: Aristomenis
authors.initials: A
authors.lastname: Thanos
authors.forename: Miin
authors.initials: M
authors.lastname: Roh
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006820:Hyaluronic Acid; D020287:In Situ Nick-End Labeling; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D017382:Reactive Oxygen Species / Q000378:metabolism; D012163:Retinal Detachment / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D020169:Caspases; D018932:Chemokine CCL2; D006820:Hyaluronic Acid; D017382:Reactive Oxygen Species; D013655:Taurochenodeoxycholic Acid; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C491766:Ccl2 protein, rat; C031655:ursodoxicoltaurine