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Analysis of the RPE Sheet in the rd10 Retinal Degeneration Model

  • Micah A. Chrenek
  • Nupur Dalal
  • Christopher Gardner
  • Hans GrossniklausGrossniklaus
  • Yi Jiang
  • Jeffrey H. Boatright
  • John M. NickersonEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

The normal RPE sheet in the C57BL/6J mouse is subclassified into two major tiling patterns: a regular generally hexagonal array covering most of the surface and a “soft network” near the ciliary body made of irregularly shaped cells. Physics models predict these two patterns based on contractility and elasticity of the RPE cell, and strength of cellular adhesion between cells. We hypothesized and identified major changes in RPE regular hexagonal tiling pattern in rd10 compared to C57BL/6J mice. In rd10 mice, RPE sheet damage was extensive but occurred later than expected, after most retinal degeneration was complete. RPE sheet changes occur in zones with a bullseye pattern. In the posterior zone, around the optic nerve, RPE cells take on larger irregular and varied shapes to maintain an intact monolayer. In mid periphery, RPE cells have a compressed or convoluted morphology that progress into ingrown layers of RPE under the retina. Cells in the periphery maintain their shape and size until the late stages of the RPE reorganization. The number of neighboring cells varies widely depending on zone and progression. RPE morphology continues to deteriorate after the photoreceptors have degenerated. The RPE cells are bystanders to photoreceptor degeneration in the rd10 model, and the collateral damage to the RPE results in changes in morphology as early as 30 days old. Quantitative measures of the tiling patterns and histopathology detected here were scripted in a pipeline written in Perl and Cell Profiler (an open source MatLab plugin) and are directly applicable to RPE sheet images from noninvasive fundus autofluorescence (FAF), adaptive optics confocal scanning laser ophthalmoscope (AO-cSLO), and spectral domain optical coherence tomography (SD-OCT) of patients with early stage AMD or RP.

Keywords

Retinal pigment epithelium RPE Morphometrics rd10 Degeneration Zona occludens 1 

Notes

Acknowledgments

The authors would like to acknowledge the support from the following organizations: NIH R01EY014026, R01EY016470, NIH R24EY017045, NIH P30EY06360, Research to Prevent Blindness, and Foundation Fighting Blindness.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Micah A. Chrenek
    • 1
  • Nupur Dalal
    • 1
  • Christopher Gardner
    • 1
  • Hans GrossniklausGrossniklaus
    • 1
  • Yi Jiang
    • 2
  • Jeffrey H. Boatright
    • 1
  • John M. Nickerson
    • 1
    Email author
  1. 1.Department of OphthalmologyEmory UniversityAtlantaUSA
  2. 2.Theoretical DivisionLos Alamos National LaboratoryLos AlamosUSA

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