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Landmark 3-D Model Feature 69 biO-OphthalmOlOgy floating aggregates of ESCs and of retinal differentiation from similar ESCs however, formation of retinal epithelial structures was not happening. A key step in the process that led to the successful self-assembly was the addition of FormationLaNDM of self-assemblingARK retina 3-D from embryonicMoD steme cellsL basement-membrane matrix components – matrigel – to support the formation of a stable epithelial structure. is a ‘game changer’ According to Prof Sasai, without the matrigel, “cells tend to fall apart,” presumably due to the absence of the by Gearoid Tuohy mechanical support which would be available under normal organogenesis in vivo. Given the significant cost and timelines involved in developing new therapeutic strategies, the availability of 3-D emarkable research has shown for the first time models could provide a considerable resource in accelerating the formation of a three-dimensional retina in a the testing of new compounds. laboratory dish beginning with no more than a Furthermore, one of the significant challenges in culture of floating embryonic stem cells. tackling disorders such as retinitis pigmentosa is that as While sounding more like science fiction than fact, the R time progresses the patient loses first rod and then cone breakthrough is set to fundamentally impact on both academic photoreceptors which are not replaced. Any viable treatment studies of retinal biology and on the pharmacological testing needs to apply a potential therapy to a dwindling number of new compounds and treatment strategies for a broad range of photoreceptors. If the RIKEN research successes can be of retinal disorders, including retinitis pigmentosa and age- replicated in the development of self-assembling 3-D human related macular degeneration (AMD). retinas then clinicians and patients may benefit from a The self-assembly of a murine retina from 3-dimensional renewable source of photoreceptors to be transplanted at an cultures of embryonic stem cells is among the most complex optimal development stage. tissue engineering achievements yet. While of immediate Dr Eriaku and Prof Sasai commented that “self-formation interest to the field of ophthalmology, the advance has of fully stratified 3-D neural retina tissues heralds already made an impact on stem cell biology and regenerative The self-assembly of a murine retina from 3-dimensional cultures of embryonic stem the next-generation of generative medicine in retinal medicine, disciplines keen to explore the potential application cells is among the most complex tissue engineering achievements yet. The success, reported from the Organogenesis and Neurogenesis Group at the RIKEN Center for degeneration therapeutics, and opens up new avenues for of the research for brain and other tissues. Developmental Biology, is likely to have a fundamental impact on both research and drug the transplantation of artificial retinal tissue sheets, rather Research data showed that the use of embryonic stem cells development in the field of retinal medicine than simple cell grafting.” Projecting such technology in assembly of the retina emerged spontaneously in vitro onto the broad landscape of many other degenerative suggesting the capability of self-assembly may be applied to becomes discernible, and between days 20 to 24, the full disorders, while many years away, may open numerous new many other organs and, as such, may radically alter not only neuro-sensory retina is complete with photoreceptors, all in approaches for treatment. basic research but also the cost and development timelines their correct anatomical location. While the medical and research applications of the for introducing new drugs for retinal degenerations. While the lab-based self-assembly appeared to follow studies are destined to attract much commentary, the The researchers behind the new development, Dr the natural temporal sequence of retinal formation and evolutionary context of the findings is notable. The eye Mototsugu Eiraku and Prof Yoshiki Sasai of the RIKEN the differentiated cells appeared to be organised into the has long represented a major battlefield in historical and Center for Developmental Biology, in Kobe, Japan, correct cellular layers, whether or not the organ functions in contemporary debates on evolution by natural selection. published their findings in the journal Nature [2011;472:51- capturing and processing light inputs remains to be tested. If, as the argument goes, such a slow gradual piecemeal 56]. In a series of time-lapse images of laboratory culture Regardless, the supplementary videos accompanying the paper process underlies the formation of organs of such exquisite – available on the Nature website (www.nature.com) – are in themselves worth viewing if only to see first-hand the perfection as the human eye, then what use was there for the self-assembling retina begins as a floating “cloud” of incredible assembly of one of the body’s most complex organs. the endless varieties that preceded the finished product in embryonic stem cells (ESCs) which, in the presence of A number of research groups around the world had humans? matrigel, begins to express genes known to be markers of the previously shown retinal differentiation from ESCs and the While modern scientific thought universally accepts that retinal fate. formation of lens-like structures and retinal rosettes from a half an eye or even a fraction of an eye is fundamentally Within approximately six days, the cloud becomes a variety of studies all of which were homing in on defining better than none at all, we witness in the RIKEN research, hollow sphere containing polarised epithelial cells. Specific the illusive elixir of protocols and culture conditions aimed unfolding frame by frame, the ontogeny of a mammalian cells self-associate into islands that form vesicles that at optimising the development of more organised tissues. eye in a laboratory dish. We see several million years of eventually involute to the classic C shape of the developing The RIKEN research team themselves have demonstrated evolution condensed into 24 days – for this alone the studies retina. A rudimentary retinal pigment epithelium slowly the self-formation of cerebral cortical tissues in culture from are destined to represent a major scientific landmark. Jazz For Sight A charity jazz concert featuring ophthalmologists Thomas The upcoming show will be their reunion. The concert will Pfleger and Dan Reinstein will be held in Vienna on Monday support the help organisation "Light for the World” and is 19 September. sponsored by CROMA. Dan Reinstein, who lives and works in London and is The lineup of musicians are: Dan Reinstein (sax); Thomas internationally known in the field of refractive surgery, and Thomas Pfleger (guitar), Vana Gierig (piano), Matthew Parrish (bass), Pfleger, who is an ophthalmologist in Vienna, are experienced jazz Joris Dudli (drums), Jose Brito (perc), special guest: Jacqueline musicians. Together with Vana Gierig, who is one of New York’s Patricio (vocal). premier jazz pianists and composers, they will perform at Porgy & Bess Jazz & Music Club, one of the top venues on the European n Monday, 19 September, 20.30, Porgy & Bess, jazz scene. Riemergasse 11, A 1010 Vienna. Drs Reinstein and Pfleger met in 1998 for the first time when they Admission: €18. Thomas Pfleger Dan Reinstein performed together with Vana Gierig in Fort Lauderdale, US. EUROTIMES | Volume 16 | Issue 9.
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