April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Studying the pathophysiology of Choroideremia through a patient-specific iPSc-derived RPE
Author Affiliations & Notes
  • Marie Pequignot
    Inserm U1051, Montpellier, France
  • Nicolas Cereso
    Inserm U1051, Montpellier, France
  • Cecile Hilaire
    Inserm U1051, Montpellier, France
  • Christian P Hamel
    Inserm U1051, Montpellier, France
  • Vasiliki Kalatzis
    Inserm U1051, Montpellier, France
  • Footnotes
    Commercial Relationships Marie Pequignot, None; Nicolas Cereso, None; Cecile Hilaire, None; Christian Hamel, None; Vasiliki Kalatzis, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1344. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Marie Pequignot, Nicolas Cereso, Cecile Hilaire, Christian P Hamel, Vasiliki Kalatzis; Studying the pathophysiology of Choroideremia through a patient-specific iPSc-derived RPE. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1344.

      Download citation file:

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

  • Supplements

Purpose: A growing number of retinal dystrophies lack an appropriate small animal model,compromising further comprehension of the pathophysiology. In such cases, a viable alternative wouldbe to perform studies on human cellular models of the diseased retina. As a pilot project, we generateda human cellular model of the X-linked disease choroideremia (CHM). CHM represents 2% of retinaldystrophies and is characterised by night blindness in childhood leading to blindness by 50 y of age. Itis due to mutations in the CHM gene encoding Rab escort protein 1 (REP1). Knock-out mouse andzebrafish REP1-deficient models are lethal.

Methods: To generate a pertinent human cellular model, we reprogrammed REP1-deficient fibroblastsfrom a CHM-/y patient into induced pluripotent stem cells (iPSc). We then differentiated thesepatient-specific iPSc into REP1-deficient retinal pigment epithelium (RPE).

Results: The iPSc-derived CHM RPE is a monolayer that expresses RPE-specific markers, ispolarised, and has tight junctions. Ultra-structural studies demonstrate the presence of microvilli onthe surface and a characteristic RPE subcellular organisation. We are currently studying thedifferences in fluid transport, phagocytosis, melanosome trafficking and visual cycle differencesbetween wild type and patient RPE.

Conclusions: We generated a bona fide RPE from a CHM patient, showing that the iPSc-derivedcellular models can potentially be used to better understand the pathophysiology of retinal dystrophieslacking an appropriate animal model.

Keywords: 636 pathobiology • 701 retinal pigment epithelium • 695 retinal degenerations: cell biology  

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.