Retinopathies
Team :
Christelle Monville : Professor (UEVE)
Alexandra Alarza : Qualified research technician (CECS)
Alexandra Plancheron : Qualified research technician (CECS)
Céline Lustrémant : PhD Student
An orphan or rare disease is generally considered to have a prevalence of less than 1/1000 affected individuals. Although this may appear as of minor importance, most of these diseases have a poor prognosis and their number is so high (several thousands) that it represents a major public health problem. Thereby, therapeutics of these genetic disorders denotes a genuine challenge in research. These include diseases of the developing neural system. The general project of this team was first to develop and improve cell therapy protocols for three monogenic disorders: (i) retinopathies and (ii) X-fragile syndrome.
The second axis of the team project is based on the fact that hES and iPS (induced pluripotent stem cell) cell lines which express a disease-related mutant gene could represent a relevant cellular model. We have used this approach to perform a pathological model of Congenital Leber Amaurosis (CLA), for which we are developing iPS cells carrying the mutation. By comparing native and mutant hES cell lines, we aim to identify biomarkers which present alterations associated with the mutation. In the first part of this project, we aim to differentiate hES cells into a cell population committed to the neural and retinal program. This part is developed in parallel to the obtention of cell therapy protocols for retinal diseases. The second part of the project will be dedicated to the validation of these biomarkers. This will be the starting point of physiopathological analyses and to a large scale drug-screening.
Retinal diseases are associated with the loss of photoreceptors, which are specialised neurons. It affects about 1:3000 individuals worldwide. Inheritance forms of retinal degeneration are highly focused on gene mutations within photoreceptors leading to devastating loss of visual function, often leading to blindness.
In the context of cell therapy, the ability of human embryonic stem cells (hESCs) to be expanded indefinitely in culture whilst retaining their pluripotent status suggests that these cells could be used as an unlimited source of partially or fully differentiated retinal cells for tissue transplantation and cellular therapy. The recent discovery that is possible to directly reprogram somatic cells to an ESC-like pluripotent state, known as induced pluripotent stem (iPS) cells, offer a great potential use in regenerative medicine. Furthermore, the generation of iPS cells from an individual patient would enable the large-scale production of the cell types affected by the patient’s disease. These cells could in turn be used for disease modelling, drug discovery and autologous cell replacement therapy.
The principal aims of this project will attempt (i) to generate functional photoreceptor progenitors from hESCs and iPS cells and (ii) to study photoreceptors alterations, in two pathologies, RP and CLA (Congenital Leber Amaurosis), using mutated hESC/iPS cell lines. 
