Researchers hit the bull's EYE

By Angela C.H. McDonald

Generating complex organ tissue from pluripotent stem cells is a major challenge in the field of regenerative medicine. Significant progress has been made in directing pluripotent stem cells to differentiate into specific cell types however; there have been few examples of the successful production of organ tissue in vitro. Last month, a group of researchers from Japan reported in Nature the remarkable generation of optic cup tissue from mouse embryonic stem cells in a dish.

Following 8-10 days of culture in defined retinal inducing conditions and in the presence of extracellular matrix proteins, embryonic stem cells differentiated to form three-dimensional structures that molecularly and morphologically resemble optic cup tissue in vivo. Using an embryonic stem cell line containing a fluorescent reporter gene expressed in the developing eye, researchers captured the elegant morphogenetic process of optic cup formation in a dish using live imaging. Stunning videos demonstrate the outpouching of embryonic stem cell aggregates and their subsequent morphological movements that result in an optic cup, recapitulating mammalian eye development. 

This new tool has developmental biologists excited about the possibility of elucidating molecular interactions that orchestrate eye development as well as the possibility of isolating stage-specific progenitor cells throughout optic cup development. 

But what does this research mean for patients suffering from degenerative eye disease?  The authors anticipate that application of this technology to human pluripotent stem cell lines could open up the possibility of generating artificial retinal tissue sheets for transplantation. 

Many eye diseases including age-related macular degeneration result from degeneration of retinal tissue. Following disease or injury, the human retina does not regenerate, leaving an individual with impaired vision. For patients suffering from degenerative eye disease, tissue transplantation is the only hope for regaining lost sight.  

There is reason to be optimistic about the potential of embryonic stem cell-derived retinal cells to treat eye disease. In fact, a number of groups around the world are working to move their stem cell technologies forward into clinical trials. However, stem cell therapy holds an array of challenges including the ability to coax transplanted cells into forming complex functional tissue layers. 

In April, Chinese and American researchers published their results following the transplantation of rod photoreceptors derived from swine induced pluripotent stem cells into swine retina in the journal Stem Cells. While the survival of a small number of injected cells and their subsequent differentiation into a mature morphology is exciting, there was no functional improvement in electrophysiological response to light. In contrast, transplantation of fetal retinal tissue into human patients can restore some visual acuity however ethical and supply issues hamper the use of fetal transplants as a viable therapeutic option. Optic cup tissue generated from pluripotent stem cells in vitro is an intriguing alternative.

While the generation of optic cup tissue in a dish from mouse embryonic stem cells is exciting, much more work needs to be done before we can think about therapeutic applications, beginning with the transfer of this technology to human pluripotent stem cells.

Why should regenerative medicine efforts focus in part on eye regeneration? Well for starters, one million Canadians have some form of age-related macular degeneration. According to the Canadian National Institute for the Blind, more Canadians have age-related macular degeneration than breast cancer, prostate cancer, Parkinson’s or Alzheimer’s disease combined. The economic impact of eye disease is staggering -– the National Coalition for Vision Health reports the cost of vision loss in 2007 as $15.8 billion, which includes direct health care costs as well as the indirect costs of lost productivity, welfare and other expenses. By 2032, this figure is expected to double, making a need for therapies even more pressing.