Purchase this article with an account.
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)
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.
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).
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.
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.
This PDF is available to Subscribers Only