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Retinal & Corneal Degeneration

Retinal Degeneration

There is real potential that people with certain blinding diseases of the retina might in the future benefit from transplantation of retinal cells or of cells that are able to deliver survival or “rescue” factors to the retinal cells in vivo. Basic science and clinical translational research groups are focussing their attention on generating and characterising different types of stem cells, deriving retinal cells from them in culture, and testing their potential to rescue or support retinal function after transplantation into the eye. There are very promising reports emerging that in animal studies and in some clinical cases, there is measurable improvement in vision after stem cell transplantation (see Ong and da Cruz, 2012, Jang et al, 2012 for recent reviews) or sheets of retinal cells (Seiler and Aramant 2012).

There has been a convergence of interests that has brought together a group of cell biologists, human geneticists and ophthalmologists at UCT who have worked together for a number of years on the genetics and cell biology of some retinal degenerative conditions. In order to be able to study disease processes in a dish, test drugs and ultimately to create suitable cell lines that might be used therapeutically, it is necessary to obtain donor cells from individuals with inherited retinal degenerative conditions. Our group has been able to advance rapidly on work on deriving iPS from various groups of patients. We have received training from experts at Stem Cell Institute in Singapore (S H Kidson, in 2011) and in Oxford (R Ballo and L Watson, 2011 and 2012). We are using the most advanced methods for deriving these cells, and have been successful in obtaining and characterising iPS lines from patients with the retinal degenerative disease SCA-7, and from normal unaffected family members. We are currently using the retrovirus or Sendai virus reprogramming protocols and obtained a number of cells lines (Ballo, Watson and Smith) , and have further characterised them in terms of their pluripotency, morphology and genetic stability (Watson, PhD thesis). We have also succeeded in differentiating the iPS cells into retinal pigment epithelial cells (D Smith, PhD studies) and into neurons (Watson).

The corneal endothelium and blindness

Light enters the eye through the cornea, and is focused by the lens onto the back of the eye where it stimulates receptor cells which allow us to see. The cornea consists of three layers, the outermost epithelium, the stroma in the middle and the corneal endothelium (CE). The CE is pivotal in maintaining this transparency. A variety of diseases, infections or even old age can lead to corneal damage and because the adult CE is unable to proliferate (divide) and regenerate the CE barrier is compromised, becomes dysfunctional and this ultimately leads to an opaque cornea and consequent blindness. One potential solution to this problem is to carry out corneal transplants. However there is a worldwide shortage of donor corneas and addition there is a post-transplantation a loss of cells which has the potential to lead to an opaque cornea redeveloping with subsequent blindness. Thus there is much effort worldwide to develop solutions to the problem of blindness arising from corneal damage and opacity.

The use of stem cells to treat blindness resulting from corneal endothelial damage

One approach to solve the problem of corneal damage is to make use of cells, either precursor cells or stem cells to form a new CE. To achieve this, one needs to understand how cells (such as stem cells) can be induced to form a functional CE. Ultimately it might be possible to use tissue engineering in cultures, with the aim of forming corneas for transplantations. The broad aim of our studies are to explore whether the CE can be created from stem cells in vitro (Dennis Lin, PhD studies) and 2) to explore whether there are cells in the cornea with stem cell-like properties that can be reactivated/stimulated to self regenerate in vitro. (Dr EL van der Merwe)