Shedding light on glaucoma causal mechanisms, genes and cell types
Ayellet Segrè, PhD, an Assistant Professor of Ophthalmology at Harvard Medical School, and Genetic Biostatistician at the Ocular Genomics Institute at Mass. Eye and Ear (MEE), and her lab members, in collaboration with Janey Wiggs, MD, Ph.D., Ocular Genomics Institute Associate Director, and Professor of Ophthalmology at HMS, Josh Sanes, Professor of MCB at Harvard University, and the International Glaucoma Genetics Consortium published a paper in January 9, 2024, in Nature Communications: https://www.nature.com/articles/s41467-023-44380-y, on prioritizing regulatory mechanisms, genes, pathways, and cell types affecting primary open-angle glaucoma (POAG) and intraocular pressure (IOP), through integrative genetic and functional genomic analyses of ocular and non-ocular tissues. Combining GWAS of POAG and IOP with genetic regulation of gene expression and splicing (e/sQTLs) and single cell expression across a range of eye tissues proposed hundreds of genes whose dysregulation may affect glaucoma risk, and highlighted specific cell types that may play an important role in glaucoma pathogenesis in an IOP-dependent or independent manner, such as fibroblasts in the conventional and unconventional aqueous humor outflow pathways, astrocytes in retina and optic nerve head, and fibroblasts in the surrounding region of the optic nerve head. This work provides multiple hypotheses for functional follow ups and may inform the development of new IOP reducing and neuroprotective therapies.