We have a new Webvision chapter on Retinal Degeneration, Remodeling and Plasticity! Check it out here.
Lasker/IRRF Report On Restoring Vision
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
Portrait Of Vision Scientist: Ann Morris
Ann Morris from the University of Kentucky studies the zebrafish (Danio rerio). In particular, she studies the ability of zebrafish retinas to regenerate following retinal injury or damage. Retinal regeneration is an interesting phenomenon that mammalians seem to lack and yet zebrafish manage to do this despite having a retina that in many ways is far more complex than the mammalian retina.
Ann talks about her work in the following video from the University of Kentucky: Continue reading “Portrait Of Vision Scientist: Ann Morris”
The Judgment Of Solomon
I had the honor and privilege of attending a Lasker/IRRF Initiative’s plenary session on Restoring Vision to the Blind at Janelia Farm last month where Mr. Sanford D. Greenberg delivered an emotional and inspiring story of a time in his life where he lost his vision during his junior year at Columbia University. The prospect of losing vision is absolutely and completely life altering for those affected as well as for those around the individual who has lost partial or complete sight. Mr. Greenberg’s story in his words, reveals the raw emotion of blindness, the fear and angst as well as the compassion and love of those who travel through life alongside us. At the end, there is also a surprise that will speak to aficionados of music and give some deeper insight into someone who has touched untold millions around the globe through their work and music.
This video is documentation of that event sent along for Webvision to share with you and the wider community by John Dowling the Chair of the Lasker/IRRF Initiative, and Janelia Farm who captured the video, the Lasker Foundation, the International Retinal Research Foundation and End Blindness by 2020. We are grateful to Mr. Greenberg for sharing his story and allowing us to help spread his story and mission of ending blindness here on Webvision.
On a personal note: While I have friends who are blind or are going blind, Mr. Greenberg’s talk haunted me the night after I saw it, particularly because of the field of science I am engaged in. Every scientist studying vision and diseases affecting vision should have the opportunity to spend time with those who have lost sight. It is important for people in the sciences to sit down and talk with those affected by the disease they study. I found this out this week after a meeting with a colleague who agreed to speak with a mutual friend who has Usher’s Syndrome. When my colleague stated after the meeting that they had never actually sat down to talk with someone who has the disease that they study, I was initially surprised. This is not uncommon though. As scientists, not just in the vision sciences mind you, we obsess about the details of what we study and are absolutely driven by the work, but do not always look around and talk with people who’s diseases are the subjects of our studies. This is fundamental to the process as it drives home the motivation for the long hours, late nights and frustrations with grant funding. It forces an introspection and helps us to better communicate our work to a wider audience which is critical to science progress and funding.
Notable Papers: An Easier Way To Make 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.
Continue reading “Notable Papers: An Easier Way To Make Stem Cells?”
Interesting Article: Mechanism of RPE Cell Death in α-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux
I ran across an interesting paper in PLOS One published back in March of 2012 by Parameswaran G. Sreekumar, Christine Spee, Stephen J. Ryan, Susan P. C. Cole, Ram Kannan and David R. Hinton. This manuscript looks at a mechanism of retinal pigment epithelium (RPE) cell death with notable findings identifying therapeutic targets for disorders that involve the RPE cells.
The authors tested whether α-crystallin has a protective effect that is influenced by changes in glutathione (GSH) content while exploring the mechanism of glutathione efflux from the cells. Interestingly, they found that the multiple multidrug resistance proteins (MRP) were expressed in RPE, particularly MRP1 and that it is MRP1 that mediates GSH (reduced form) and GSSG (oxidized form) efflux from the RPE cells. In addition, they noted that inhibition of MRP1 makes RPE cells resistant to oxidative stress induced cell death pathways and conversely, over expression of MRP1 renders them more susceptible to oxidatively induced cell death pathways. Finally the authors note that α-crystallin’s antiapoptotic function is mediated by both GSH and MRP1.
Moran Eye Center International Outreach
Here on Webvision, our goal is retinal education and even though Webvision is hosted here at the Moran Eye Center, we nevertheless try to include as much of the wider community as possible in posts and in content, though we will point out work that comes of of the Moran Eye Center from time to time. So, while we compiling chapters for information as well as posts to the front page here that we hope contain informative items relevant to the retina and the retinal research community, it is important from time to time to step back and ask why it is that we study the retina and get a bigger picture view of what role all of this biology plays in peoples lives.
Full-Length Axon Regeneration In The Adult Mouse Optic Nerve and Partial Recovery of Simple Visual Behaviors
Friend of Webvision Yves Sauvé sent in this paper by Silmara de Lima, Yoshiki Koriyama, Takuji Kurimoto, Julia Teixeira Oliveira, Yuqin Yin, Yiqing Li, Hui-Ya Gilbert, Michela Fagiolini, Ana Maria Blanco Martinez, and Larry Benowitz that documents regeneration of the optic nerve in the adult mouse, a potentially substantial breakthrough in therapeutic recovery of vision lost through disease or trauma.
Photovoltaic Retinal Prosthesis With High Pixel Density
Retinas are complex systems and engineered rescues of vision loss through bionic means have to date been inelegant solutions. Retinal bionic implants have historically not been successes due to some glaring problems including how to power them and how to get the appropriate current close enough to the cells to induce a response. However, researchers at Stanford University and University of California, Santa Cruz have now developed a photovoltaic retinal prosthesis that is wirelessly powered which eliminates one of the biggest hurdles on the viability of bionic Continue reading “Photovoltaic Retinal Prosthesis With High Pixel Density”
Dysmorphic Photoreceptors in a P23H Mutant Rhodopsin Model of Retinitis Pigmentosa Are Metabolically Active and Capable of Regenerating to Reverse Retinal Degeneration
This paper (and the cover article) is the result of a collaborative effort between Damian C. Lee, Felix R. Vazquez-Chona, W. Drew Ferrell, Beatrice M. Tam, Bryan W. Jones, Robert E. Marc, and Orson L. Moritz.
Notable Paper: Gene Therapy Rescues Photoreceptor Blindness in Dogs and Paves The Way for Treating Human X-linked Retinitis Pigmentosa
This paper in PNAS by William A. Beltran, Artur V. Cideciyan, Alfred S. Lewin, Simone Iwabe, Hemant Khanna, Alexander Sumaroka, Vince A. Chiodo, Diego S. Fajardo, Alejandro J. Román, Wen-Tao Deng, Malgorzata Swider, Tomas S. Alemán, Sanford L. Boye, Sem Genini, Anand Swaroop, William W. Hauswirth, Samuel G. Jacobson and Gustavo D. Aguirre is a continuation of their work in retinal degeneration, this form of retinal degeneration, X-linked retinitis pigmentosa (RP).
Notable Paper: Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model
Hereditary retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophies, macular degeneration) are characterized by loss of visual function, sometimes starting during early childhood, other times in late adulthood. About 30% of these dystrophies are inherited in an autosomal dominant fashion (RetNet), caused by gain-of-function mutant alleles which encode a malignant form of a normal protein. Continue reading “Notable Paper: Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model”
Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function
This paper by Vazquez-Chona FR, Swan A, Ferrell WD, Jiang L, Baehr W, Chien WM, Fero M, Marc RE and Levine EM addresses a long standing issue in the field of neuroscience: is the reactive phenotype of glial cells in and of itself detrimental to neural survival or function?
Retinoid Receptors Trigger Neuritogenesis in Retinal Degenerations
This paper by Y Lin, BW Jones, A Liu, JF Tucker, K Rapp, L Luo, W Baehr, PS Bernstein, CB Watt, JH Yang, MV Shaw and RE Marc examines the neuronal sprouting or neuritogenesis components of retinal remodeling found in retinal degenerative disease and describes a control process for retinoid X receptors (RXRs) in neuritogenesis. Continue reading “Retinoid Receptors Trigger Neuritogenesis in Retinal Degenerations”
Notable Paper: Virally Delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness
This truly groundbreaking paper by M Mehdi Doroudchi, Kenneth P Greenberg, Jianwen Liu, Kimberly A Silka, Edward S Boyden, Jennifer A Lockridge, A Cyrus Arman, Ramesh Janani, Shannon E Boye, Sanford L Boye, Gabriel M Gordon, Benjamin C Matteo, Alapakkam P Sampath, William W Hauswirth and Alan Horsager demonstrates that channelrhodopsin-2, a cation channel from algae than can be gated/activated by light can restore both physiological and behavioral visual responses in mice with retinal degenerative disease.