title: Aceruloplasminemia: retinal histopathologic manifestations and iron-mediated melanosome degradation.
abstract: OBJECTIVE
  To examine the retinal histopathologic manifestation of aceruloplasminemia, an autosomal recessive disease caused by mutation of the ferroxidase ceruloplasmin, resulting in tissue iron overload.
  
  
  METHODS
  The morphologic features of the human aceruloplasminemic retina were studied with light and electron microscopy. Retinal iron accumulation was assessed with Perls Prussian blue staining, immunohistochemistry, and secondary ion mass spectrometry.
  
  
  RESULTS
  Light and electron microscopic analysis revealed several ocular pathologic findings that resembled age-related macular degeneration, including retinal pigment epithelium (RPE) depigmentation, atrophy and hypertrophy, nodular and diffuse drusen, and lipofuscin and melanolipofuscin granules. Complement deposition was detected in drusen. The RPE cells and neural retina had increased levels of iron. Two major types of RPE cells were observed: melanosome rich and melanosome poor. Melanosome-rich cells had increased levels of iron and melanolipofuscin. The melanolipofuscin granules were observed in large aggregates, where some of the melanosomes were degrading. Melanosome-poor cells lacked melanosomes, melanolipofuscin, and lipofuscin but contained electron-dense aggregates high in iron, phosphorus, and sulfur.
  
  
  CONCLUSIONS
  The findings in the aceruloplasminemic retina resemble some of those found in age-related macular degeneration. Also, they suggest that melanosomes in the RPE can be degraded via iron-mediated reactive oxygen species production.
  
  
  CONCLUSIONS
  Mechanisms underlying the pathologic mechanisms found in aceruloplasminemia also may be important in age-related macular degeneration.
authors.affiliation: F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Wolkow
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Ting-Di
authors.initials: TD
authors.lastname: Wu
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Guerquin-Kern
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
mesh_terms: D000369:Aged, 80 and over; D002570:Ceruloplasmin / Q000172:deficiency / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D019189:Iron Metabolism Disorders / Q000378:metabolism / Q000473:pathology*; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology; D008297:Male; D020460:Melanosomes / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D018629:Spectrometry, Mass, Secondary Ion; D013194:Staining and Labeling / Q000379:methods; D014168:Transferrin / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism
chemical_list: D015938:Complement Membrane Attack Complex; D008062:Lipofuscin; D014168:Transferrin; D019096:Vitronectin; D005293:Ferritins; D002570:Ceruloplasmin
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