Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Modeling retinitis pigmentosa with iPS cells

Retinitis pigmentosa (RP) is a cluster of genetically determined eye disorders that cause visual defects such as night blindness and narrowing of the field of vision, due to progressive loss of rod photoreceptors. New work by Zi-Bing Jin and colleagues looks to add a set of powerful new tools for those searching for treatments for RP.

Retinitis pigmentosa (RP) is a cluster of genetically determined eye disorders that cause visual defects such as night blindness and narrowing of the field of vision, due to progressive loss of rod photoreceptors. As many as 45 different genes have been linked to the inheritance of this disease, which suggests diversity in etiology and makes development of a standardized animal model problematic. Thus, despite a range of clinical trials of nutritional and drug-based interventions for RP, the disease remains untreatable. Better platforms for modeling the disease and testing drug candidates in vitro are urgently needed.

New work by Zi-Bing Jin and colleagues in the Laboratory for Retinal Regeneration (Masayo Takahashi, Team Leader) looks to add a set of powerful new tools for those searching for treatments for RP. In an article published in PLoS One, the team reports the generation of induced pluripotent stem cells (iPSCs) from patients carrying mutations in several RP-associated genes, and the subsequent differentiation and characterization of rod photoreceptors from these genetically distinct, patient-derived pluripotent cells.

After obtaining informed consent from five RP patients with distinct mutations in the RP1, RP9, PRPH2, or RHO gene, the team took samples of skin cells and used the fibroblasts as a starting point for generating iPSCs. Using the classic reprogramming cocktail of Oct4, Sox2, Klf4, and c-Myc delivered via a retroviral vector, Jin and colleagues generated cell lines from each patient and verified their conversion by tests for appropriate morphology, genetic and karyotypic integrity, and teratoma formation.

Using these iPSCs, the team next generated photoreceptors carrying the genetic signatures of each of the five patient donors using a previously established stepwise protocol that steered the cells over four months in culture from an undifferentiated ES cell-lie state through retinal progenitor, and photoreceptor precursor stages to the desired rod photoreceptor phenotype. The differentiated cells were shown to express the rod photoreceptor marker rhodopsin at high levels, and to have similar electrophysiological function.

Interestingly, rod photoreceptor cells generated from iPSC colonies carrying RP-linked mutations showed a tendency to degenerate, while cone photoreceptors and bipolar cells derived from the same iPSCs were stable. The mechanisms underlying this instability turned out to be dependent on the affected gene. Rod photoreceptors generated from iPSCs with a mutation in the RP9 gene showed evidence of DNA oxidation, while those from iPSCs with a mutation in the rhodopsin gene showed signs of stress on the endoplasmic reticulum, the site of protein synthesis.

As an initial proof-of-concept test of their suite of RP-specific rod photoreceptors in drug validation, Jin and colleagues examined the effects of antioxidant vitamins in preventing degeneration of these cells in vitro. Ascorbic acid, á-tocopherol, and â–carotene have all been tested in clinical trials as anti-oxidant therapies for RP, but all had not proved very effective. When the team tested these on individual cells lines by treating them with one of the three antioxidants for seven days at around the stage at which rod photoreceptor degeneration occurs, they found that á-tocopherol increased cell survival in the lines generated from two patients both carrying mutations in RP9. The same treatment was ineffective in cells from other patients, and ascorbic acid and â–carotene had no effect in any of the lines. These results, which show the efficacy of á-tocopherol in promoting survival in RP9 rod photoreceptors, highlights the potential of patient-derived induced pluripotent stem cells in the study of disease mechanisms and in vitro testing of treatment approaches.

“Using iPSCs from cells donated by RP patients with different underlying genetic mutations, we were able to show that rod photoreceptors generated from these cells underwent apoptosis in vitro, and showed differing responses in a genetically determined manner to drug treatment,” says Takahashi. “This is one of the first reports to demonstrate that patient-derived iPSCs may be useful in personalized medicine, as differential responses within a genetically diverse study group will tend to be lost in the crowd. Future improvements in differentiation protocols, screening techniques, cost and efficiency and the establishment of methods for isolating photoreceptors may open up new possibilities for the use of these cells in drug screening.”

[ Contact ]
Douglas Sipp : sipp(at)
TEL : +81-78-306-3043
RIKEN CDB, Office for Science Communications and International Affairs

Patient-derived rod photoreceptors undergo degeneration in vitro. The bars show differentiation efficiencies of the iPS cells derived from five retinitis pigmentosa patients.

Journal information
PLoS One. 2011 Feb 10;6(2):e17084.
Modeling retinal degeneration using patient-specific induced pluripotent stem cells.

Jin ZB, Okamoto S, Osakada F, Homma K, Assawachananont J, Hirami Y, Iwata T, Takahashi M.

gro-pr | Research asia research news
Further information:

More articles from Life Sciences:

nachricht Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH

nachricht Bioluminescent sensor causes brain cells to glow in the dark
28.10.2016 | Vanderbilt University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Steering a fusion plasma toward stability

28.10.2016 | Power and Electrical Engineering

Bioluminescent sensor causes brain cells to glow in the dark

28.10.2016 | Life Sciences

Activation of 2 genes linked to development of atherosclerosis

28.10.2016 | Life Sciences

More VideoLinks >>>