Examination of the TrkB receptor signalling pathway throughout the retina of glaucoma patients versus age-matched controls.
- Type of funding: Fight for Sight Small Grant Award
- Grant Holder: Dr Andrew Osborne
- Institute: University of Cambridge
- Region: East of England
- Start date: April 2018
- End Date: December 2019
- Priority: Treatment
- Eye Category: Glaucoma
Glaucoma is a group of eye disorders that leads to progressive visual loss and eventually blindness. This occurs due to retinal ganglion cells (RGCs) dying gradually. The survival of RGCs is usually maintained with the help of brain-derived neurotrophic factor survival (BDNF) and its receptor, tropmyosin-related receptor kinase B (TrkB).
Studies in animal models of glaucoma have shown that there is disrupted transport of BDNF and TrkB from the brain to the eye. There is also some evidence that BDNF levels are reduced in the tears and serum of glaucoma patients.
Researchers have designed a novel gene therapy to restore BDNF and TrkB levels in patients with glaucoma. This project will improve our understanding of BDNF signalling in human retinal tissue.
Little is known about the specific expression of BDNF and TrkB within human RGCs but previous studies have shown overall levels of TrkB signalling in the retina are reduced with glaucoma. The researchers will measure the number of surviving RGCs in post-mortem retinal tissue from subjects with glaucoma versus age-matched controls. They will also measure the level of BDNF and TrkB receptors across the retinas and identify cell types which exhibit immunolabelling.
Researchers will verify these changes to shed light on why RGCs are shifted from a cell survival state to one that undergoes cell death. The discovery of differences in BDNF signalling molecules between glaucoma patients and controls would provide additional support and justification for therapies that enhance BDNF signalling in glaucoma patients. These findings would help ensure the gene therapy concepts we are currently developing target the correct cells and should help treat patients with progressive glaucoma even with intraocular pressure lowering treatment.