Lasker/IRRF Report On Restoring Vision

Restoring Vision To The Blind

I participated in the Lasker/IRRF Initiative on Restoring Vision to the Blind in March 2014. It was a great session of research leaders working on various approaches to restore visual function lost by retinal degenerative disease. The purpose of the meeting was to identify the key issues hampering research progress and to develop innovative proposals to overcome these hurdles and accelerate research. The Initiative prepared a report of its findings that ARVO published as a special edition of its online journal Translation Vision Science and Technology. It can be viewed at http://tvstjournal.org/toc/tvst/3/7.

I am attaching the Table of Contents for the report, along with John Dowling’s introduction to give you an idea of the scope of the work discussed by participants.  If you want a pdf of the entire report, you can find it on the Lasker website at: http://www.laskerfoundation.org/programs/images/irrf_15.pdf . A print copy of the report is also available by writing to Meredith Graves as mgraves@laskerfoundation.org

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Notable Papers: An Easier Way To Make Stem Cells?

Stem Cells

We’ve talked about work out of the RIKEN Institute before here on Webvision.  The work that comes out of there is clever and often unconventional.  The latest work from the RIKEN that seems to have gotten a bit of attention is two recent papers from Haruko Obokata and colleagues, here and here that discuss almost inconceivably simple approaches to generating stem cells out of adult, differentiated blood, fat, muscle and brain mouse cells.  The approach essentially immerses the cells in an acidic solution for a half hour to induce a state of cell stress and subsequent induced pluripotency allowing them to recapitulate mature, differentiated tissues of a variety of cell types, including a reported blastocyst.  Granted, there are a variety of ways to collect and harvest stem cells, but these approaches present a variety of both ethical and logistical confounds.  So, this approach could solve a number of problems related to collecting and harvesting stem cells.

The other notable thing about this study is how elegant the screening method was.  The authors used GFP tagged Oct4 genes to note when cells had reached pluripotent status.  These GFP expressing cells were then indicators of induced pluripotency in harvested, differentiated cells that underwent stress through acid immersion.  Since only approximately 25% of the cells that underwent acid immersion survived, this approach allowed the investigators to see which of those remaining cells exhibited Oct4 gene expression revealing pluripotent stem cell status.  Other assays backed up these determinations of pluripotency including teratoma assays as well as the creation of chimeras.

If this approach proves a viable technique to generating stem cells, work in stem cell based vision rescuing therapeutics (as well as many other therapeutic applications) could be dramatically facilitated as labs exploring stem cell therapies in vision rescue are currently having to invest large efforts in using existing approved stem cell stocks or isolating stem cells through labor intensive methods.

Update 03/10/14:

The Wall St. Journal is reporting that one of the co-authors of this study said the research contained “crucial mistakes” and RIKEN is weighing whether to retract the papers.

 

Update 07/02/2014:

Nature has announced that the papers have been retracted.

 

Update 09/23/2015:

The STAP approach has been completely refuted.

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Notable Papers: Self-organizing optic-cup morphogenesis in three-dimensional culture

I was blown away by this paper out of the Sasai laboratory at the Riken Center for Developmental Biology.  Essentially, the Sasai laboratory is trying to recapitulate the developmental process of the retina in a test tube in isolation from the rest of the live animal.  Its a stunning development that appears to demonstrate bilayered optic vesicles, then cups that reach around to surround the lens vesicle.  Many efforts to grow organs in a dish have been attempted before, going back to the 1990’s, and eye development studies have been performed in frogs to get eyes to grow in places they do not normally develop, but this is the first time such a complex tissue/organ has been apparently successfully demonstrated in culture conditions.  The advance from the Sasai laboratory specifically demonstrates that the evagination of the optic vesicle can be induced and controlled to form a bilayered cup (from this Webvision page, animation here).  This process normally requires the surrounding tissues to provide guidance and induction cues, so engineering this to happen spontaneously from homogeneous pluripotent cells in culture is a substantial advance.

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