Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells

Sallyanne Davies, Michael H. Elliott, Eric Floor, T. George Truscott, Mariusz Zareba, Tadeusz Sarna, Farrukh A. Shamsi, Michael E. Boulton

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Lipofuscin accumulates with age in a variety of highly metabolically active cells, including the retinal pigment epithelium (RPE) of the eye, where its photoreactivity has the potential for cellular damage. The aim of this study was to assess the phototoxic potential of lipofuscin in the retina. RPE cell cultures were fed isolated lipofuscin granules and maintained in basal medium for 7 d. Control cells lacking granules were cultured in an identical manner. Cultures were either maintained in the dark or exposed to visible light (2.8 mWcm2) at 37°C for up to 48 h. Cells were subsequently assessed for alterations in cell morphology, cell viability, lysosomal stability, lipid peroxidation, and protein oxidation. Exposure of lipofuscin-fed cells to short wavelength visible light (390-550 nm) caused lipid peroxidation (increased levels of malondialdehyde and 4-hydroxy-nonenal), protein oxidation (protein carbonyl formation), loss of lysosomal integrity, cytoplasmic vacuolation, and membrane blebbing culminating in cell death. This effect was wavelength-dependent because light exposure at 550 to 800 nm had no adverse effect on lipofuscin-loaded cells. These results confirm the photoxicity of lipofuscin in a cellular system and implicate it in cell dysfunction such as occurs in ageing and retinal diseases.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalFree Radical Biology and Medicine
Volume31
Issue number2
DOIs
StatePublished - Jul 15 2001

Keywords

  • A2E
  • Free radicals
  • Light damage
  • Lipofuscin
  • Lysosomes
  • Oxidation
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Davies, S., Elliott, M. H., Floor, E., Truscott, T. G., Zareba, M., Sarna, T., Shamsi, F. A., & Boulton, M. E. (2001). Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radical Biology and Medicine, 31(2), 256-265. https://doi.org/10.1016/S0891-5849(01)00582-2