• Open Access

Genetic Basis of Inherited Macular Dystrophies and Implications for Stem Cell Therapy§


  • Carla B. Mellough,

    1. Institute of Human Genetics andInternational Centre for Life, Newcastle Upon Tyne, United Kingdom
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  • David H.W. Steel,

    1. Sunderland Eye Infirmary, Queen Alexandra Road, Sunderland, Tyne and Wear, United Kingdom
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  • Majlinda Lako

    Corresponding author
    1. North East Stem Cell Institute, Newcastle University, International Centre for Life, Newcastle Upon Tyne, United Kingdom
    • Newcastle University, Institute of Human Genetics and NESCI, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ
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    • Telephone: 0-191-241-8688; Fax: 0-191-241-8666

  • Author contributions: C.B.M.: Manuscript writing; D.H.W.S.: Manuscript writing and fund raising; M.L.: Manuscript writing and fund raising.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS June 23, 2009; available online without subscription throught the open access option.


Untreatable hereditary macular dystrophy (HMD) presents a major burden to society in terms of the resulting patient disability and the cost to the healthcare provision system. HMD results in central vision loss in humans sufficiently severe for blind registration, and key issues in the development of therapeutic strategies to target these conditions are greater understanding of the causes of photoreceptor loss and the development of restorative procedures. More effective and precise analytical techniques coupled to the development of transgenic models of disease have led to a prolific growth in the identification and our understanding of the genetic mutations that underly HMD. Recent successes in driving differentiation of pluripotent cells towards specific somatic lineages have led to the development of more efficient protocols that can yield enriched populations of a desired phenotype. Retinal pigmented epithelial cells and photoreceptors derived from these are some of the most promising cells that may soon be used in the treatment of specific HMD, especially since rapid developments in the field of induced pluripotency have now set the stage for the production of patient-derived stem cells that overcome the ethical and methodological issues surrounding the use of embryonic derivatives. In this review we highlight a selection of HMD which appear suitable candidates for combinatorial restorative therapy, focusing specifically on where those photoreceptor loss occurs. This technology, along with increased genetic screening, opens up an entirely new pathway to restore vision in patients affected by HMD. STEM CELLS 2009;27:2833–2845