A2E, A Pigment of RPE Lipofuscin, is Generated from the Precursor, A2PE by a Lysosomal Enzyme Activity

  • Janet R. Sparrow
  • So Ra Kim
  • Ana M. Cuervo
  • Urmi Bandhyopadhyayand
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

The lipofuscin that accumulates in retinal pigment epithelial cells with age and that is abundant in some retinal disorders, is sequestered within the interior of membrane bound organelles of the lysosomal compartment of the cell. RPE lipofuscin pigments form in large part due to reactions of vitamin A aldehyde.


Retinal Pigment Epithelial Cell Outer Segment Photoreceptor Outer Segment Human Retinal Pigment Epithelium Protease Inhibitor Mixture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ben-Shabat S, Parish CA, Vollmer HR, Itagaki Y, Fishkin N, Nakanishi K, Sparrow JR. 2002, Biosynthetic studies of A2E, a major fluorophore of RPE lipofuscin. J Biol Chem 277: 7183–7190.PubMedCrossRefGoogle Scholar
  2. Cuervo AM, Dice JF, Knecht E. 1997, A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272:5606–5615.PubMedCrossRefGoogle Scholar
  3. Feeney-Burns L, Eldred GE. 1983, The fate of the phagosome: conversion to ‘age pigment’ and impact in human retinal pigment epithelium. Trans Ophthalmol Soc U K 103:416–421.PubMedGoogle Scholar
  4. Fishkin N, Pescitelli G, Sparrow JR, Nakanishi K, Berova N. 2004, Absolute configurational determination of an all-trans-retinal dimer isolated from photoreceptor outer segments. Chirality 16:637–641.PubMedCrossRefGoogle Scholar
  5. Fishkin NE, Pescitelli G, Itagaki Y, Berova N, Allikmets R, Nakanishi K, Sparrow JR. 2004, Isolation and characterization of a novel RPE cell fluorophore: all-trans-retinal dimer conjugate. Invest Ophthalmol Vis Sci 45:E-abstract 1803.Google Scholar
  6. katz ML, Drea CM, Eldred GE, Hess HH, Robison WG, Jr. 1986, Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium. Exp Eye Res 43:561–573.PubMedCrossRefGoogle Scholar
  7. Katz ML, Redmond TM. 2001, Effect of Rpe65 knockout on accumulation of lipofuscin fluorophores in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 42:3023–3030.PubMedGoogle Scholar
  8. Liu J, Itagaki Y, Ben-Shabat S, Nakanishi K, Sparrow JR. 2000, The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2PE, in the photoreceptor outer segment membrane. J Biol Chem 275:29354–29360.PubMedCrossRefGoogle Scholar
  9. Lorenz B, Wabbels B, Wegscheider E, Hamel CP, Drexler W, Presing MN. 2004, Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. Ophthalmol 111:1585–1594.CrossRefGoogle Scholar
  10. Ohsumi Y, Ishikawa T, Kato K. 1983, A rapid and simplified method for the preparation of lysosomal membranes from rat liver. J Biochem 93:547–556.PubMedGoogle Scholar
  11. Parish CA, Hashimoto M, Nakanishi K, Dillon J, Sparrow JR. 1998, Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. Proc Natl Acad Sci U S A 95:14609–14613.PubMedCrossRefGoogle Scholar
  12. Salvador GA, Giusto NM. 1998, Characterization of phospholipase-D activity in bovine photoreceptor membranes. Lipids 33:853–860.PubMedCrossRefGoogle Scholar
  13. Storrie B, Madden E. 1990, solation of subcellular organelles. Methods Enzymol 182:203–225.PubMedCrossRefGoogle Scholar
  14. Young RW. 1971, The renewal of rod and cone outer segments in the rhesus monkey. J Cell Biol 49:303–318.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Janet R. Sparrow
    • 1
  • So Ra Kim
  • Ana M. Cuervo
    • 2
  • Urmi Bandhyopadhyayand
    • 2
  1. 1.Departments of OphthalmologyPathology and Cell Biology, Columbia UniversityNew York
  2. 2.Department of Anatomy and Structural BiologyAlbert Einstein College of MedicineBronx

Personalised recommendations