CAREER: An integrated platform to understand neurodegeneration in glaucoma blindness

Glaucoma is one of the leading causes of irreversible blindness worldwide. This disease can progress unnoticed until vision loss occurs. This CAREER project aims to create innovative tools to unlock how glaucoma affects the nerve cells in the eye and to explore ways to detect and treat the disease earlier. The research includes developing a model that mimics glaucoma in animal eyes, using non-invasive technology to monitor nerve health, and applying advanced computer programs to analyze the data. These efforts will help uncover the cause of glaucoma and identify early signs of the disease. The educational aspect of this project will promote eye health awareness through hands-on workshops for K-12 students and new online resources, such as videos that teach at-home eye exercises. The project also includes developing teaching modules for college students to foster a learning environment accessible to all students. Through partnerships with local schools, industry, and community programs, this work aims to inspire future scientists, engineers, and healthcare professionals while contributing to new solutions for glaucoma care. This CAREER project aims to address key gaps in understanding glaucoma-induced neurodegeneration by developing an integrated platform combining bioengineering tools and neurobiological studies. The platform will include (1) an injectable microbead-based in vivo flow occlusion model to replicate glaucoma-like conditions and achieve sustained intraocular pressure (IOP) elevation, (2) a non-invasive electroretinogram (ERG) recording system to monitor retinal neural activity longitudinally, and (3) artificial intelligence (AI)-assisted algorithms for unbiased analysis of electrophysiological data. These tools will be applied to investigate the mechanisms driving retinal ganglion cell (RGC) degeneration and disruptions in lateral inhibition within the retina’s vision signal transduction pathway. The project will focus on optimizing biointerfaces in the flow occlusion model for reliable IOP elevation, advancing ERG systems for continuous monitoring of neural changes, and using AI to identify early-stage glaucoma biomarkers. Additionally, pharmacological and genetic regulation of specific inhibitory neuron populations will be combined with ERG and IOP monitoring to study how hyperactivation of inhibitory neurons contributes to RGC loss. The resulting platform will provide insights into the cellular and molecular mechanisms of glaucoma, enabling earlier detection and identifying potential therapeutic targets. This integrated approach aims to improve outcomes for glaucoma patients and advance technologies for vision science. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.