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UCL Institute of Ophthalmology

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Prof Rachael Pearson

Prof Rachael Pearson

Professor of Developmental Neuroscience

Institute of Ophthalmology

Faculty of Brain Sciences

Joined UCL
1st Dec 2002

Research summary

Retinal degenerations culminating in photoreceptor (PR) loss are the leading causes of untreatable blindness in the Western world. Clinical treatments are of limited efficacy, at best slowing disease progression. As such, there is a clear need for new therapeutic approaches. Gene therapy is effective in the treatment of inherited retinal disease. However, such strategies will be ineffective once degeneration has occurred. PR transplantation offers a complementary approach that could not only halt the progression of blindness but also potentially reverse it. In two landmark studies, we have demonstrated that, by using donor cells from early postnatal retina, PR cell transplantation is possible. The adult retina is capable of integrating transplanted cells & these cells develop unambiguous characteristics of mature PRs. Moreover, we the cells that possess this capacity to migrate & functionally integrate are post-mitotic PR precursors, rather than stem or progenitor cells (MacLaren & Pearson et al., Nature, 2006). Most importantly, we now have definitive evidence of restoration of rod-mediated visually-guided behaviour in rod-deficient mice following transplantation (Pearson et al., Nature, 2012). Together, these establish a major proof-of-concept; that PR transplantation has the potential to improve not only retinal function but actually restore vision and provide strong justification for the continued research into photoreceptor transplantation strategies for the treatment of blindness. They also increase the need to find appropriate donor cells from non-fetal sources. Recent advances in stem cell technology have demonstrated the potential to generate PR donor cells from ES cells (Eiraku et al.,2011; West et al., Stem Cells, 2012). Current projects 1) Defining new strategies to restore cone-mediated vision. We have demonstrated that it is possible to restore vision mediated by rods but humans rely heavily upon cones for vision in daylight and colour-vision. For this reason, we aim to define new strategies for the restoration of cone-mediated vision by transplantation. 2) Determine the mechanisms of migration utilized by both rod and cone precursors in normal development and following transplantation. By understanding how the small proportion of cells transplanted manage to migrate into the recipient retina, we should be able to find ways to manipulate this migration and drive more cells into the recipient retina. 3) Determine strategies for breaking down barriers within the recipient retina. We have recently examined transplantation efficiency in a variety of models of retinal degeneration and found that disease type has a major impact on outcome (Barber et al., in press). On going work aims to identify factors within the degenerating retina that impede (or enhance) transplanted cell integration and find ways to manipulate them to improve transplantation outcome (West et al., 2012; Pearson et al., 2010; West et al., 2008) 4) Determine whether purinergic signalling is an evolutionarily restricted signalling mechanism in the control of retinal stem cell proliferation. Unlike lower vertebrates, the mammalian retina lacks the ability to generate. Understanding the mechanisms behind these differences is crucial to knowing whether it might be possible to stimulate the mammalian retina to repair itself.

Teaching summary

PhD supervision:

Miss Amanda Barber (2009-2012); 

Miss Katherine Warre-Cornish (Wellcome 4 yr PhD Neuroscience; 2009-2012); 

Mr Paul Waldron (Wellcome 4 yr Phd Neuroscience; 2012-) 

Miss Anna Graca (MRC Clinical Neuroscience PhD; 2012-)

Mr Dominic Aghaizu (UCL Grand Challenge PhD Studentship; 2012-)

MSc supervision:
Mr Haydar Hussain (2010); 
Mr Ka Tong (2012); 
Mr Angshu Angbohang (2012); 
Mr Kareem Mahgoub (2012)

BSc supervision: 
Katlyn Green (2012)

Lecturing: MSc Biology of Vision, MSc Neuroscience, BSc Developmental Neurobiology 

Education

University College London
PhD, Neuroscience | 2002
University of Oxford
BA Hons, Physiological Science | 1999
Publications