title: Translocation of the retinal pigment epithelium and formation of sub-retinal pigment epithelium deposit induced by subretinal deposit.
abstract: OBJECTIVE
  A cardinal pathological feature of age-related macular degeneration (AMD) is the deposition of extracellular material between the retinal pigment epithelium (RPE) and Bruch's membrane, pathologically described as sub-RPE deposits. Both the presence and local organization of these deposits contribute to the clinical manifestations of AMD, including localized deposits clinically recognized as drusen. The biogenesis of sub-RPE deposits remains elusive. This work explores the pathological processes of sub-RPE deposit formation.
  
  
  METHODS
  Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Tissue sections were examined by light or confocal microscopy.
  
  
  RESULTS
  In the presence of the subretinal deposit of Matrigel, RPE cells leave Bruch's membrane to migrate toward photoreceptors and then form a new layer between the deposit and photoreceptors, resulting in RPE translocation. The new RPE layer displaces the deposit to the sub-RPE location and therefore it becomes a sub-RPE deposit. The RPE mobilization requires the presence of photoreceptors. Bruch's membrane devoid of RPE attachment becomes vulnerable to invasion by new blood vessels from the choroid.
  
  
  CONCLUSIONS
  Our work supports a novel model of sub-RPE deposit formation in which excessive material first accumulates in the subretinal space, disrupting the physical contact between RPE cells and photoreceptors. To restore the contact, RPE cells migrate toward photoreceptors and form a new layer. The subretinal material is consequently displaced to the sub-RPE location and becomes sub-RPE deposit. Our data also provide evidence that the presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Alan M
authors.initials: AM
authors.lastname: Laties
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
mesh_terms: D000818:Animals; D002465:Cell Movement; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000473:pathology; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D007797:Laminin; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D011509:Proteoglycans; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D015593:Retinal Drusen / Q000473:pathology*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen