Representative transmission electron microscopic image of retinal ganglion cell packed with dysfunctional organelles following loss of functional autophagy.

Projects:

1. Developing non-viral delivery of genome editors to trabecular meshwork: We are currently exploring lipid nanoparticles mediated mRNA delivery of genome editing complex to the trabecular meshwork. We plan to target glaucoma gene, myocilin (MYOC), which is known cause glaucoma in Children’s and adults. Using this technology, we hope to cure glaucoma.
2. Lipid nanoparticles mediated anti-sense oligos therapy for glaucoma: Using lipid nanoparticles carrying anti-sense oligos, we are developing therapy for juvenile glaucoma caused by MYOC mutation.
3. Small molecules targeting ER stress and autophagy for the treatment of glaucoma: we have shown that small molecular, sodium 4-phenylbutyrate (PBA) rescues mouse models of glaucoma by reducing ER stress and improving autophagy. We are currently developing ocular therapy for the treatment of all forms of glaucoma.
4. The role of autophagy in neuronal homeostasis and in glaucoma: By selectively knocking out autophagy genes in various neuronal cell types including RGCs, astrocytes and glial cells in the eye, we are exploring the basal function of autophagy in neuronal homeostasis and function.
5. Single cell transcriptome analysis of trabecular meshwork in glaucoma: Using recently developed mouse models of primary open angle glaucoma and human donor eyes from normal and glaucoma patients, we are utilizing single cell transcriptome to understand the pathology of glaucoma.
6. Targeting axonal transport deficits in glaucoma: Our studies show that impaired axonal transport precedes glaucomatous neurodegeneration. We are currently exploring various treatment strategies to improve axonal transport to protect dying RGCs.

Immunostaining for astrocyte marker, GFAP and retinal ganglion cell marker, RBPMS in mouse retina. The lab focuses on understanding how autophagy in astrocytes and retinal ganglion cells is critical for neuronal function and survival in glaucoma.