title: Metallothionein-III deficiency exacerbates light-induced retinal degeneration.
abstract: OBJECTIVE
  Retinal photoreceptor damage is a common feature of ophthalmic disorders, such as age-related macular degeneration and retinitis pigmentosa. Oxidative stress has a key role in these diseases. Metallothioneins (MTs) are a family of cysteine-rich proteins, and various physiologic functions have been reported, including protection against metal toxicity and antioxidative potency. We investigated the functional role of MT-III in light-induced retinal damage.
  
  
  METHODS
  The expression of retinal MT-I, -II, and -III mRNA was evaluated by real-time reverse-transcription PCR in retina exposed to light. Retinal damage in MT-deficient mice was induced by exposure to white light at 16,000 lux for 3 hours after dark adaptation. Photoreceptor damage was evaluated histologically by measuring the thickness of the outer nuclear layer (ONL) 5 days after light exposure and by electroretinogram recording. In an in vitro experiment, the MT-III siRNAs were tested for their effects on light-induced mouse photoreceptor cell (661W) damage.
  
  
  RESULTS
  The mRNAs of the MTs were increased significantly in murine retina after light exposure. The ONL in the MT-III-deficient mice was remarkably thinner compared to light-exposed wild-type (WT) mice, and a- and b-wave amplitudes were decreased; the damage induced in MT-I/-II-deficient mice was comparable to that observed in WT mice. MT-III knockdown by siRNA in 661W exacerbated the cell damage and increased the production of reactive oxygen species in response to light exposure.
  
  
  CONCLUSIONS
  These findings suggested that MT-III can help protect against light-induced retinal damage compared to MT-I/II. Some of these effects may be exerted by its antioxidative potency.
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Inoue
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Imai
authors.forename: Jinyong
authors.initials: J
authors.lastname: Lee
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005786:Gene Expression Regulation; D008027:Light / Q000009:adverse effects; D008297:Male; D008668:Metallothionein; D000090023:Metallothionein 3; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics*; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008668:Metallothionein