The role of matrix metalloproteinase-3 in retinal ganglion cell survival and regeneration: insights from mouse models of optic neuropathies.

Glaucomatous optic neuropathies (GONs) form a group of clinically similar eye diseases, which are characterized by progressive optic nerve fiber degeneration and loss of retinal ganglion cells (RGCs), resulting in irreversible blindness. Lowering intraocular pressure (IOP) is currently the only treatment to prevent disease progression. However, despite a successful IOP control, some patients continue losing vision. This emphasizes the need to further unravel the underlying pathophysiological events and contributing molecules. MMP-3 belongs to the matrix metalloproteinase family and is known to contribute to neurological disorders. Using two mouse models for GONs and a novel approach to induce axonal regeneration of damaged RGCs, we aim to unravel the role of this proteinase in influencing RGC survival and axonal outgrowth. Loss of RGCs, the accompanying degenerative and inflammatory processes as well as their regenerative capacities will be evaluated by morphological and functional analyses in MMP-3 deficient mice. Underlying substrates and mechanisms will be investigated using proteomic identification and loss function approaches, respectively. These studies will advance our knowledge on the mechanisms underlying neurodegeneration in the eye and on ways to induce neuroprotection and axonal regeneration of RGCs. As such, this research project may significantly improve the visual prognosis of our ageing population that is increasingly suffering from blinding diseases.