Increased Pressure in Eye Affects the Neuronal Communications in the Brain
Detailed Non-Technical Summary
We aim to study the effects of OHT on synaptic dysfunction coupled with autophagy impairment in mouse model of glucocorticoid (GC)-induced glaucoma as well as human normal and primary open angle glaucoma (POAG) donor eyes. In Aim1, we will determine the effect of OHT on synaptic dysfunction during the progression of glaucomatous neurodegeneration. In Aim2, we will determine the crosstalk between autophagy impairment and synaptic pathology and determine whether enhancing autophagy restores synaptic function and alleviate glaucomatous neurodegeneration.
Glaucoma is a neurodegenerative disease, in which the entire visual pathway including retina, optic nerve (ON) and visual centers of the brain gets affected due to chronic intraocular pressure (IOP) elevation. This proposal will utilize GC-induced glaucoma and RGC specific autophagy mouse models to decipher the impact of IOP induced autophagy impairment on axonal synaptic function and retrograde cellular changes. We will further understand whether enhancing autophagy restores synaptic function and alleviate glaucomatous neurodegeneration.
The methods and outcomes from this project will increase our understanding of IOP induced autophagy impairment and its effect on neuronal communications in the brain. On successful completion of this study, we will provide important insight into the underlying molecular mechanisms of glaucomatous neurodegeneration, and highlight novel therapeutics based on autophagy-inducing strategies for the treatment of glaucoma.