Cells form tissues by adhering to each other via large molecular complexes called cell-cell junctions. These junctions are essential for the development, function and maintenance of all tissues including the retina. p114RhoGEF is a protein which functions as a regulator to control the assembly of cell-cell junctions. Complete inactivation of p114RhoGEF is lethal before birth.
Mutations in the gene that encodes for p114RhoGEF lead to a partial inactivation of the function of the protein, have been identified in patients with retinitis pigmentosa. As such diseases only become apparent after birth or even only in adulthood, partially inactive p114RhoGEF is sufficient for the development of functional organs and tissues, but not for their long-term maintenance. The underlying reasons that lead to retinal degeneration and blindness are not known.
Retinitis pigmentosa can originate from defects in at least two cell types: photoreceptors, the cells that sense light, and the cells of the retinal pigment epithelium, a layer of cells that supports photoreceptor function and survival. Both of these engage in cell-cell junctions and defects in p114RhoGEF may affect either of them.
Researchers aim to identify the molecular mechanisms by which defective p114RhoGEF leads to malfunctioning of cell-cell junctions in retinal pigment epithelial cells and photoreceptors, and how such defects lead to degeneration of these cell types.
Cells from healthy control donors and from patients carrying defective p114RhoGEF will be used to generate specific retinal cell types. How mutations in this gene alter their structural and functional properties will be investigated. These cells will be used to determine if and how defective p114RhoGEF affects the cell structure and shape, using microscopy to visualise specific cellular components that are important for the function of these cells.
Once the underlying mechanisms have been identified, therapeutic approaches can be designed to decrease or stop retinal degeneration. As different mutations may affect the cells by similar mechanisms, this study may contribute to the development of new treatments for different forms of retinal degenerations.
Mutations in the gene that encodes for p114RhoGEF lead to a partial inactivation of the function of the protein, have been identified in patients with retinitis pigmentosa. As such diseases only become apparent after birth or even only in adulthood, partially inactive p114RhoGEF is sufficient for the development of functional organs and tissues, but not for their long-term maintenance. The underlying reasons that lead to retinal degeneration and blindness are not known.
Retinitis pigmentosa can originate from defects in at least two cell types: photoreceptors, the cells that sense light, and the cells of the retinal pigment epithelium, a layer of cells that supports photoreceptor function and survival. Both of these engage in cell-cell junctions and defects in p114RhoGEF may affect either of them.
Researchers aim to identify the molecular mechanisms by which defective p114RhoGEF leads to malfunctioning of cell-cell junctions in retinal pigment epithelial cells and photoreceptors, and how such defects lead to degeneration of these cell types.
Cells from healthy control donors and from patients carrying defective p114RhoGEF will be used to generate specific retinal cell types. How mutations in this gene alter their structural and functional properties will be investigated. These cells will be used to determine if and how defective p114RhoGEF affects the cell structure and shape, using microscopy to visualise specific cellular components that are important for the function of these cells.
Once the underlying mechanisms have been identified, therapeutic approaches can be designed to decrease or stop retinal degeneration. As different mutations may affect the cells by similar mechanisms, this study may contribute to the development of new treatments for different forms of retinal degenerations.