title: Deletion of Efemp1 Is Protective Against the Development of Sub-RPE Deposits in Mouse Eyes.
abstract: EFEMP1 (fibulin-3) is mutated in Malattia Leventinese/Doyne's honeycomb retinal dystrophy (ML/DHRD), an inherited macular dystrophy similar to AMD. Both ML/DHRD and AMD are characterized by the presence of sub-RPE deposits. Efemp1 knockout mice do not develop sub-RPE deposits. This study was to test whether sub-RPE deposits can be induced in Efemp1 knockout mice by experimentally applied stress conditions that cause wild-type mice to develop sub-RPE deposits.
  
  
  
  Efemp1 knockout and control mice at 6, 18, or 24 months old were fed with a synthetic high-fat diet (HFD). Beginning 1 month after starting the HFD, one group of mice was exposed to cigarette smoke daily for 1 month, and another group of mice was subjected to photochemical injury every other day for 2 weeks from a 488-nm argon laser. After the treatments, histologic analysis was performed to assess whether sub-RPE deposits were induced.
  
  
  
  Basal laminar deposits (BLamDs), a form of sub-RPE deposits, were observed in the 18- and 24-month-old wild-type mice but not in Efemp1 knockout mice in any age groups after exposure to HFD and cigarette smoke or laser injury.
  
  
  
  Mice lacking fibulin-3 do not develop sub-RPE deposits. Environmental oxidative stressors (HFD/cigarette smoke or HFD/laser) known to cause BLamD formation in wild-type mice failed to induce BLamD formation in Efemp1 knockout mice. These results suggest that fibulin-3 is a central player in the development of BLamD, and deletion of fibulin-3 is protective against the development of BLamD.
authors.affiliation: Department of Ophthalmology & Vision Science, University of Arizona, Tucson, Arizona, United States.
authors.forename: James B
authors.initials: JB
authors.lastname: Stanton
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Marmorstein
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Lihua Y
authors.initials: LY
authors.lastname: Marmorstein
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005500:Follow-Up Studies; D017353:Gene Deletion; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: C492278:Efemp1 protein, mouse; D016326:Extracellular Matrix Proteins; D004247:DNA