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Laboratory science
Topography of neuron loss in the retinal ganglion cell layer in human glaucoma
  1. Y Lei1,
  2. N Garrahan2,
  3. B Hermann1,
  4. M P Fautsch3,
  5. D H Johnson3,
  6. M R Hernandez4,
  7. M Boulton5,
  8. J E Morgan1
  1. 1
    Optometry and Vision Sciences, Cardiff University, Cardiff, UK
  2. 2
    Pathology, University Hospital Wales, Cardiff, UK
  3. 3
    Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA
  4. 4
    Department of Ophthalmology, Northwestern University, Chicago, Illinois, USA
  5. 5
    Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida, USA
  1. Correspondence to Mr J E Morgan, School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4LU, UK; morganje3{at}cardiff.ac.uk

Abstract

Aim: To determine if retinal ganglion cell (RGC) loss influences the loss of surrounding RGCs to generate clustered patterns of cell death in human glaucoma. It is hypothesised that retinal ganglion cell loss accelerates the loss of surrounding cells to generate, at a local, cellular scale, clustered patterns of retinal of RGC death. The absence of these interactions would result in a diffuse pattern RGC loss.

Method: Six glaucomatous retinas (67–83 years old) and six age-matched control retinas (61–89 years old) were prepared as wholemounts and stained by 4′,6-diamidino-2-phenylindole (DAPI) solution (3 μg/ml in PBS). An area corresponding to central 14° of the visual field was imaged. The nearest-neighbour distribution was determined for cells in both normal and glaucomatous RGCL.

Results: Clustered RGC loss in human glaucoma was observed on a background of diffuse loss. The mean nearest-neighbour distance (NND) of the glaucomatous retinas was significantly higher than with controls (p<0.001). The distribution of NND in glaucomatous retinas was skewed to the higher values with a higher positive kurtosis relative to controls. The quantitative analysis of the pattern of cell loss is supported by the visual inspection of the patterns of cell loss.

Discussion: The nearest-neighbour analysis is consistent with the presence of two patterns of cell loss in the RGCL in glaucoma. While the diffuse of cell loss can account for an overall reduction in the RGC population, an additional non-random pattern is consistent with the hypothesis that RGC loss has a local influence on the viability of surrounding cells.

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Footnotes

  • Funding Supported by Research Into Ageing, UK (grant no 127). The retrieval of glaucoma eyes was supported by NIH EY 15736 (MPF), NIH EY 07065 (MPF, DHJ).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by Cardiff University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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