We discovered that transplantation and subsequent restoration of visual function is possible, but only when the donor cells are at a specific stage of development: that is when they are already committed to a photoreceptor fate (Figure 2).31. First, the inner retinal neurons are already born in the late developing retina and may interfere with photoreceptors trying to reconnect to the host inner nuclear layer. However, it should not be assumed that the treatment is effective, as it is not possible to say whether these improvements would be sustained in the long term. A full-thickness sheet of foetal retina presents a physical challenge to photoreceptor viability. A number of studies have investigated retinal transplantation of various types of stem cells. Neuronal specification is guided by complex interactions between intrinsic (genetic) programs and extrinsic regulatory factors, and requires the precise coordination between exit from the cell cycle and differentiation.32, 33, 34 A transcription factor is a small DNA-binding protein that acts as a genetic switch to activate specific genes (Figure 3). The researchers were able to make retinal cells that were over 99% pure. Ghosh F, Ehinger B . Plasticity and tissue regenerative potential of bone marrow-derived cells. directly with human brainwaves. BBC News, January 24 2012, Once they were blind, now they see. Invest Ophthalmol Vis Sci 2004; 45: 4570–4575. Age-related macular degeneration. The discovery of a population of stem cells with neurogenic potential in the adult ciliary margin of the mouse and human eye,23, 24 raises the intriguing possibility of auto-transplantation that would avoid the problem of rejection and without cloning (see below). Gouras P, Du J, Gelanze M, Lopez R, Kwun R, Kjeldbye H, Krebs W . MacLaren RE, Bird AC, Sathia PJ, Aylward GW . Transcription factors activate developmental genes that are vital for defining the adult cell type but also have an important role in adult cell maintenance. Re-establishment of visual circuitry after optic nerve regeneration. A groundbreaking stem cell trial offers hope for millions with progressive conditions that end in sight loss, the Daily Mail has today reported. To reach this point, it will be necessary to carry out other, larger scale clinical trials to further prove the efficacy of the treatment. A further problem is that the inner part of the transplanted tissue would be ganglion cell and displaced amacrine cells. The reasons for this are not clear, but may lie in the complexity of epigenetic mechanisms, such as DNA methylation and histone acetylation.50 These DNA modifications regulate gene expression in a similar way to X chromosome inactivation, and it may be that the epigenetic changes in adult primate DNA are simply too complex to be reversed.51 In successfully cloned non-primate mammals, however, factors released by the oocyte cytoplasm appear to have remarkable control of somatic DNA, either in restoring telomere length,52 or in reprogramming of X-inactivation.53 Understanding the mechanism whereby oocyte cytoplasm controls somatic nuclear differentiation will almost certainly be the key to successful cloning of adult primate cells for auto-transplantation. Cell replacement by transplantation would be relevant to age-related macular degeneration (AMD), the single commonest cause of blindness in the UK and which causes visual impairment in about one quarter of a million people.2 Although promising new treatments for exudative AMD are being developed, such as molecular inhibition of choroidal new vessels,3 many patients will still suffer progressive photoreceptor loss, as will those with geographic atrophy. Converting stem cells into photoreceptors is a challenging area of basic science that requires considerable expertise in cloning and developmental biology. Age-related macular degeneration (AMD) is an eye condition that affects the macula, which is the central part of the retina found across the back of the eyeball. Although electronic devices are extremely effective at converting the visual image into a series of electrical impulses,1 the issue of reconnection will be paramount for restoring sight. (f) Dolly the sheep was the first mammal to be successfully cloned from an adult cell, which was taken from the mammary gland of her genetically identical mother. Progressive restriction in fate potential by neural progenitors during cerebral cortical development. The researchers followed the patients over four months but say that further follow-up is needed to observe the long-term effects of this treatment. Development 2004; 131: 5139–5152.


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