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Rachael Pearson

Dr Rachael Pearson

Dr Rachael Pearson

Research Fellow

Interests and expertise (Subject groups)

Grants awarded

Stem cell therapy and retinal degeneration

Scheme: University Research Fellowship

Organisation: University College London

Dates: Oct 2013-Feb 2017

Value: £357,154.15

Summary: Retinal diseases lead to irreversible loss of the light-detecting cells of the eye, the photoreceptors. Retinal degenerations are the leading cause of untreatable blindness in the developed world and there is a clear need for new therapeutic approaches. Replacement by the transplantation of healthy photoreceptor cells represents a way of restoring vision after the diseased photoreceptors have died. We, and others, have shown that immature photoreceptors can be transplanted into the eye, whereupon they are capable of restoring visual function in animal models of blindness. We have established protocols for the step-wise generation of immature photoreceptor donor cells from embryonic stem cells. These protocols not only provide a renewable source of donor cells for transplantation but have also provided an incredibly in vitro platform for the study of human eye development and disease, where we can grow a retina (healthy or diseased) in a dish. Much of our work to date has focused on rod photoreceptors, the cells we use in dim light conditions e.g. at dusk. However, humans use predominantly cone photoreceptors for seeing in daylight and for colour vision. We have recently determined that it is possible to transplant immature cone photoreceptors, derived both from mouse and from human embryonic stem cells, into the diseased mouse retina and it is possible for these cells to drive aspects of visual function. We have previously shown that transplantation outcome is greatly affected by the host environment and the diseased retina present a challenging environment for many therapeutic approaches. We have identified barriers within the diseased recipient retina that impede the ability of transplanted cells to contact the host retina and are determining ways of disrupting these barriers to permit greater connectivity.

Stem cell therapy and retinal degeneration

Scheme: University Research Fellowship

Organisation: University College London

Dates: Oct 2007-Sep 2013

Value: £528,433.98

Summary: Retinal diseases lead to irreversible loss of the light-detecting cells of the eye, the photoreceptors. Replacement by cell transplantation represents a way of restoring vision but, until recently, has been largely unsuccessful. There are many potential sources of donor cells, including embryonic and adult stem cells. For photoreceptor transplantation to be successful, the donor cell must be transplanted into the eye, whereupon it must migrate into the recipient retina and then mature into a functional photoreceptor that correctly wires up to the next neurons in the visual pathway. Moreover, the recipient retina and higher visual areas must be able to correctly process the information from these new cells in order to restore vision, even in severely degenerate retinae. We have shown that photoreceptor transplantation is possible if the donor cells are at a critical developmental stage; they must be photoreceptor precursor cells, or immature photoreceptors, rather than cells at other stages of development. When transplanted into diseased eyes, these cells correctly integrate within a recipient retina, form new mature photoreceptors and restore vision in animal models of blindness. We have identified barriers within the diseased recipient retina that impede transplanted photoreceptor migration, and are determining ways of disrupting these barriers to permit increased integration. We are examining how the properties of the donor cell itself influence its ability to migrate and integrate with the aim of utilising these mechanism to enable more donor cells to integrate. As there is no ready source of photoreceptor precursors for clinical application, we have also developed protocols to generate appropriate, transplantable donor cells from stem cell populations.

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