Glaucoma is the second most common cause of blindness in the UK, resulting from loss of retinal ganglion cells (RGCs). While current therapies focus on the prevention of progressive damage this project addresses the possibility of recovery of lost vision. Prior to the onset of cell death, RGCs undergo a prolonged period of degeneration in which their dendritic processes shrink. An important factor restricting adult neuronal plasticity and repair following injury is the perineuronal net (PNN), a proteoglycan matrix that surrounds neurons and their processes. Evidence that the disruption of this net can allow neurons to recover raises the prospect of its use as a therapeutic intervention.
We have developed a rat model of experimental glaucoma in which intraocular pressure (IOP) is elevated by injecting paramagnetic microspheres into the eye’s anterior chamber. This model produces gradual changes in RGCs; RGC dendritic fields will be quantified by biolistic labelling of cells with pYFP and dendritic atrophy will be quantified by Scholl analysis. We will analyse recovery of RGCs following IOP normalisation and the intravitreal injection of chondroitinase which induces partial digestion of the PNN. In pilot studies we have established that this treatment can increase RGC dendritic field area and number of branch points, but whether it can promote visual recovery in glaucoma will depend on improved RGC function. Retinas will be explanted and cultured, remaining viable for 2-3 weeks. We will employ two-photon imaging to map structural and functional RGC changes. For functional imaging, RGCs will be transduced with a calcium indicator and will be activated by temporal modulation of a stimulus of a wavelength shorter than that of the optical signal; visual response will be calculated as percentage of fluorescence change. Patch recordings from RGCs will establish whether recovering dendrites make synaptic connections with cells in the inner plexiform layer.
To be eligible to have fees paid for and receive a stipend, applicants need to be from the UK or from the EU and have lived in the UK for the last three years. EU students would only have fees paid for and no stipend. The stipend for the first year is expected to be £13, 590.
To apply you must also have achieved at least a 2:1 (or equivalent) in a degree relevant to the project. If English is not your first language you need to have achieved at least 6.5 in IELTS or equivalent.
We have developed a rat model of experimental glaucoma in which intraocular pressure (IOP) is elevated by injecting paramagnetic microspheres into the eye’s anterior chamber. This model produces gradual changes in RGCs; RGC dendritic fields will be quantified by biolistic labelling of cells with pYFP and dendritic atrophy will be quantified by Scholl analysis. We will analyse recovery of RGCs following IOP normalisation and the intravitreal injection of chondroitinase which induces partial digestion of the PNN. In pilot studies we have established that this treatment can increase RGC dendritic field area and number of branch points, but whether it can promote visual recovery in glaucoma will depend on improved RGC function. Retinas will be explanted and cultured, remaining viable for 2-3 weeks. We will employ two-photon imaging to map structural and functional RGC changes. For functional imaging, RGCs will be transduced with a calcium indicator and will be activated by temporal modulation of a stimulus of a wavelength shorter than that of the optical signal; visual response will be calculated as percentage of fluorescence change. Patch recordings from RGCs will establish whether recovering dendrites make synaptic connections with cells in the inner plexiform layer.
Funding Notes:
To be eligible to have fees paid for and receive a stipend, applicants need to be from the UK or from the EU and have lived in the UK for the last three years. EU students would only have fees paid for and no stipend. The stipend for the first year is expected to be £13, 590.
To apply you must also have achieved at least a 2:1 (or equivalent) in a degree relevant to the project. If English is not your first language you need to have achieved at least 6.5 in IELTS or equivalent.
Dead Line: 28 February 2012
