Bala Lab

Glaucoma is a neurodegerative disease that has origins in the anterior segment of the eye (pressure changes) with repurcussions on the posterior segment of the eye (retinal ganglion cells death and optic nerve degeneration). My lab is using the latest -omics methods to connect changes in the anterior segment to neurodegeneration. We are looking at this both in the context of development (congenital glaucoma) and aging (primary open angle glaucoma).

We are developing an interactome of signaling across all developing and aging ocular tissues at various ages in mice using single nucleus multiomics (RNA-seq + ATC-seq) and publicly available data sets, which we will integrate with spatial transcriptomic methods to better understand the dynamics of cell-cell interactions and influences. This will provide us with a never-before-seen "global" look at the spatiotemporal dynamics of gene expression, gene regulatory networks, transcriptional activity, and interaction partners involved in glaucoma pathogenesis. These discoveries are poised to redefine our understanding of glaucoma and will open the door to new therapies.

The trabecular meshwork (TM) and Schlemm’s canal (SC) are important tissues that regulate ocular fluid drainage and intraocular pressure (IOP). Elevated IOP is a major risk factor for glaucoma. Abnormal TM and SC developmental are contributors to early-onset glaucoma. The transcriptional control mechanisms and spatial relationships between cell types and pathways that regulate TM/SC development are poorly understood. Mutations to certain identified genes are significant causes of developmental glaucoma. Mouse models with similar mutations to those in human disease have severe TM/SC abnormalities. We aim to define the role of these genes in TM/SC development, and characterize the transcriptional regulation and molecular landscape of TM/SC development in mutant and wild type mice. We also aim to define the spatial/molecular relationships among cell types that coordinate normal development or are disrupted in mutants. We use the latest -omics methods combined with high resolution imaging and novel in vitro tools to drive at these important questions. Our research will help us learn the transcriptional control mechanisms for TM/SC development and have direct implications for improving treatments for developmental/congenital glaucoma. 

Studying Schlemm’s canal (SC) and trabecular meshwork (TM) cell biology and physiology is difficult in mouse models due to its small size and relatively inaccessible location. The endothelial cells which make up the SC are specialized and share both vascular and lymphatic traits, further making it difficult to study and manipulate. Primary TM cells tend to differentiate into fibroblasts and are not viable for long-term studies. No reliable in vitro model of the human SC and TM exists. We aim to leverage new advances in SC and TM developmental transcriptomics to create a novel in vitro model that recapitulates in vivo development and dynamics. We are working to develop a differentiation protocol of human-induced pluripotent stem cells (hiPSCs) into SC and TM cells using a cocktail of specific growth and transcription factors. This has never been done before. The creation of a cell culture system will allow us to model human mutations, perform high-throughput drug screening and testing, and ultimately develop cell replacement therapies for glaucoma.