The objective of this proposal is to study the functional role of persyn, a member of the synuclein family, under normal conditions and in glaucoma using animal and cellular models. We have selected this protein because in pilot experiments we found considerable changes in its localization and pattern of staining both in human glaucomatous optic nerve and in the optic nerve of animal models. In both cases we observed persyn immunoreactive inclusions and deposits similar to those found in brain tissues of patients with neurodegenerative diseases. The objective will be approached through the following specific aims:
Aim 1) To study the involvement of persyn in glaucomatous alterations of the retina and optic nerve using: a) a pressure induced optic nerve degeneration model considered as one of the animal models of glaucoma and b) exploring the effect of elevated hydrostatic pressure on intracellular persyn localization.
Aim 2) To determine whether overexpression of wild type and mutant persyn induces the formation of intracellular deposits and affects the viability of the cellular line of ocular origin Y79 and dopaminergic cell line MN9D. The results obtained will shed light on persyn role in molecular and cellular mechanism of neurodegeneration in glaucoma. The animal and cellular models of glaucoma that we plan to use will be a convenient tool for the study of efficiency of potential neuroprotective agents that can be used in the treatment of glaucoma.
|Surgucheva, Irina; Ninkina, Natalia; Buchman, Vladimir L et al. (2005) Protein aggregation in retinal cells and approaches to cell protection. Cell Mol Neurobiol 25:1051-66|
|Surgucheva, Irina; Park, Bum-Chan; Yue, Beatrice Y J T et al. (2005) Interaction of myocilin with gamma-synuclein affects its secretion and aggregation. Cell Mol Neurobiol 25:1009-33|
|Surgucheva, Irina; McMahan, Belinda; Ahmed, Farid et al. (2002) Synucleins in glaucoma: implication of gamma-synuclein in glaucomatous alterations in the optic nerve. J Neurosci Res 68:97-106|