April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Lipofuscin Accumulation and Autophagy in Human Lamina Cribrosa Cells
Author Affiliations & Notes
  • Elizabeth M. McElnea
    Institute of Ophthalmology, Dublin 7, Ireland
  • Barry Quill
    Institute of Ophthalmology, Dublin 7, Ireland
  • Neil Docherty
    Institute of Ophthalmology, Dublin 7, Ireland
  • Deborah M. Wallace
    Institute of Ophthalmology, Dublin 7, Ireland
  • Mustapha Irnaten
    Institute of Ophthalmology, Dublin 7, Ireland
  • Michael Farrell
    Neuropathology, Beaumont Hospital, Dublin 9, Ireland
  • Colm O'Brien
    Institute of Ophthalmology, Dublin 7, Ireland
    Ophthalmology, University College Dublin, Dublin, Ireland
  • Footnotes
    Commercial Relationships  Elizabeth M. McElnea, None; Barry Quill, None; Neil Docherty, None; Deborah M. Wallace, None; Mustapha Irnaten, None; Michael Farrell, None; Colm O'Brien, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2677. doi:
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      Elizabeth M. McElnea, Barry Quill, Neil Docherty, Deborah M. Wallace, Mustapha Irnaten, Michael Farrell, Colm O'Brien; Lipofuscin Accumulation and Autophagy in Human Lamina Cribrosa Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2677.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The intralysosomal accumulation of the non-degradable, autofluorescent macromolecule lipofuscin, impairs autophagy and may promote a decline in the function of glial cells of the lamina cribrosa which has been implicated in the pathogenesis of disease related biomechanical changes occurring at the optic nerve head (ONH) in glaucoma. This study aimed to compare levels of lipofuscin-like material in lamina cribrosa cells from normal (NLC) and glaucomatous (GLC) donor eyes and assess its effects on autophagy.

Methods: : NLC and GLC cells were examined by transmission electron microscopy (TEM) and the number of peri-nuclear lysososomes per high powered field (x 20,000) recorded. The cells were stained with Sudan Black B, and peri-nuclear lipophilic body number assessed. Cellular autofluorescence was quantified by flow cytometry (emission at 563-607nm). Real-Time PCR (RT-PCR) measured the cell content of Cathepsin D and Autophagy protein 5 (ATG5) mRNA in NLC and GLC. Cellular protein levels of the former were analysed at Western blot.

Results: : The number of peri-nuclear lysosomes was increased in GLC (11.1 +/- 3.8 v 4.2 +/- 3.7, p = 0.002) at TEM. The quantity of Sudan Black B stained peri-nuclear lipophillic bodies was also increased in GLC ( 22.10 +/- 3.57 v 13.77 +/- 5.66, p = 0.07). An increase in whole cell autofluorescence was observed in GLC ( 83062 +/- 45.1 v 41.01 +/- 3.9, p = 0.2). Cathepsin D mRNA and protein content did not differ significantly between the two cell groups. There were significantly higher levels of ATG5 mRNA in GLC samples compared to NLC.

Conclusions: : We present evidence supportive of increased lipofuscin formation as being characteristic of lamina cribrosa cells derived from donors with glaucoma with important downstream effects on autophagy. Potential future anti-glaucoma strategies might therefore include attempts at stimulation of cellular degradation systems.

Keywords: ipofuscin • lamina cribrosa • glia 

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