Multipronged Approach to Study Glaucoma-Associated Phenotypes

<p> Glaucoma refers to a group of conditions characterized by death of RGCs, increase in intraocular pressure is usually a precursor to glaucoma and irreversible optic neuropathy leads to visual impairment and blindness. Recent advances have seen a surge of new ideas and technologies to aid in the early detection, efficacious treatments and neuroprotection. Despite advances we face several challenges in understanding the pathophysiology of glaucoma. One of the many challenges scientists and ophthalmologists are facing is, to better understand IOP, its role in glaucomatous damage and design safer, more predictable IOP-lowering therapies. Another challenge is to find a practical method or develop tools to understand the molecular pathways to study RGC function and health to develop novel therapies for vision loss. This work leads to </p> <p>three complementary insights on how to address these challenges. First, we used a novel systems genetics approach to identify and validate genetic modifiers of IOP using the enlarged BXD family of strains in combination with human GWAS glaucoma cohorts. This will pave the way for improved drug development tailored to individual genotypes for POAG. Second, we have combined systems genetics, bidirectional studies using multiple species, meta-analyses, immunohistochemistry, FACS sorting and gene knockdown studies to identify and validate the identity of a genetic modulator of <em>Sncg</em>, a gene that has been previously implicated in RGC death in glaucoma. Outcomes of the investigation may provide clues to understanding the molecular mechanisms that account for the degenerative changes in RGCs in glaucoma. Third, we optimized a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC. This will allow for future careful assessment of important cell specific pathways in RGC to provide mechanistic insights into the declining of visual acuity in aged populations and those suffering from retinal neurodegenerative diseases. Taken together these studies offer a concise outlook on use of integrated systems science, molecular and imaging technologies as a needs-led innovation in ophthalmology and visual health. </p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Integrated Program in Biomedical Sciences

Year dc:date.available

2016

Author dc:creator

• Chintalapudi, Sumana Rameshbabu

Contributors dc:contributor

• Monica M. Jablonski, Ph.D.

• Flow cytometry
• Glaucoma
• Intraocular pressure
• Retina
• Retinal ganglion cells
• Systems genetics
• Medical Sciences
• Medicine and Health Sciences
• Neurosciences

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/404

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1404