April 18, 2012

expert reaction to transplantation of photoreceptors in mice

Research demonstrating the feasibility of restoring vision after retinal degeneration by transplanting photoreceptor cells was published in Nature, by demonstrating functional vision in visually impaired adult mice having undergone transplantation.

Prof Robert Aramant, (retired), University of Louisville, Dept. Ophthalmology & Visual Sciences and Visiting Researcher, University of California at Irvine, Dept. Anatomy & Neurbiology, said:

“This is an excellent paper documenting vision effects after transplantation of freshly harvested immature photoreceptors (not stem cells), using an array of sophisticated techniques ranging from the cellular to the behavioral level. However, they have omitted to reference to previous more advanced studies (of retinal progenitor sheets) more than 12 years old. By example, the light-dark shift for transducin and rod arrestin in transplanted photoreceptors shown in Fig. 1 c-f was published 1999. Many studies have shown that sheet transplants delay the deterioration of optokinetic responses and can restore visual responses by recording in the brain [3,9,10], and that synaptic connectivity between transplant and host is involved in the restoration of visual responses. This led to phase II clinical trials in Louisville, KY, in which 7 of 10 patients showed improvements in visual acuity after one year.

“In this Nature paper, all functional assessments of the transplants were done 4-6 weeks after transplantation; the authors did not look at longer term transplants because there are survival issues with transplantation of dissociated cells. The authors omit to mention that many patients with retinal degeneration, such as macular degeneration and retinitis pigmentosa, need both new photoreceptors and retinal pigment epithelium. If a patient needs new retinal epithelium it does not help how many photoreceptors are transplanted. In contrast, the advanced method to transplant retinal progenitor sheets meets these criteria and can survive long-term.

“In summary, the paper show that transplanted dissociated photoreceptors can restore vision to a small degree for a short time.”

Dr Dusko Ilic, Senior Lecturer in Stem Cell Science, Kings College London School of Medicine, said:

“The report in Nature is another example of how vision can be improved with cell-based therapy. Although the work is done in animals and transplanted cells are isolated from new-born pups, the study is a proof of concept that photoreceptor transplantation is a feasible therapeutic strategy. Ideally, photoreceptors used for transplantation would be differentiated from pluripotent stem cells and it may take some time to do that successfully on a large scale.”

Prof Phil Luthert, Director of the UCL Institute of Ophthalmology, said:

“This is a landmark paper and the techniques used here are part of a pretty big push in regenerative medicine. It was only a few years ago that we wouldn’t have thought repairing adult systems in this way would be possible – it was assumed to be a bridge too far, but with retinas at least, it seems entirely feasible.

“It is still going to be another five or ten years at least before we think about doing anything with patients, though we are now making significant progress along the way. What is truly remarkable about this field is how well transplanted cells seem to be accepted by the retina where they move into the right place and effectively wire themselves up.

“The next challenges faced by scientists in this area concern how many cells can be got into the retina, how well they can be made to connect and then to see just how effectively they will work. We also do not know how long-term any effects will be, whilst we have good reason to believe that any procedures would be long-lasting, at this stage we are only speculating.”

Prof Pete Coffey, Director of the London Project to Cure Blindness and Professor of Cellular Therapy and Visual Sciences at the UCL Institute for Ophthalmology, said:

“In this study the researchers were attempting to improve the visual ability of mice with night vision problems. By restoring or replacing photoreceptor cells they were able to improve some of these animals’ visual ability.

“This is the first report that replaces photoreceptors and recovers visual function, but it highlights the continuing issues that need to be addressed before this therapy can be used in the clinic. The problems lie with both the connectivity of the new cells and the number needed to restore function. This is a seminal paper but will still need further pre-clinical trials before we can think about restoring vision in a person.”

‘Restoration of vision after transplantation of photoreceptors’ by Pearson, R. et al., published in Nature on Wednesday 18th April.