Researchers identify genes and cell types that may have causal role in primary open-angle glaucoma formation   

Key Takeaways

• Researchers have identified key genes, biological processes, and cell types that may be important for the development of primary open-angle glaucoma (POAG).
• The work has generated new insights into POAG mechanisms, which could inform the development of novel therapies targeting intraocular pressure (IOP) reduction and neuroprotection.

Although primary open-angle glaucoma (POAG) is the leading cause of blindness in people over the age of 55, there remains no cure for the disease and its biological mechanisms are not well understood. Elevated intraocular pressure (IOP) is a major risk factor for the disease, but many patients with glaucoma have normal eye pressure and still lose vision.

In a new study published in Nature Communications, researchers from Mass Eye and Ear, led by Ayellet Segrè, Ph.D., used a variety of genetic tools to uncover key genes, biological processes, and cell types that may affect the development of POAG in IOP-dependent and independent manners. They identified hundreds of genes and regulatory effects indicating associations with POAG and/or IOP that may contribute to glaucoma risk through altered gene expression levels. (Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein. When the level of expression of a gene changes, different amounts of product are made).

The genes identified are enriched in biological pathways implicated in POAG pathogenesis, including blood vessel development and nerve cell-related processes. Furthermore, the researchers identified known and less well-established cell types in which gene dysregulation (abnormal changes in gene expression) may affect optic nerve degeneration. The pathways identified in their analysis can impact various structures in the eye, pointing to numerous potential mechanisms that can interact with different genes and cell types that may contribute to POAG.

“Our work has generated new insights into POAG mechanisms, which could inform the development of novel therapies targeting IOP reduction and neuroprotection,” said Segrè. “For example, this research suggests that targeting neuronal support cells, in addition to retinal ganglion cells, may be important to consider in the design of new drug and cell therapies. Through our ongoing work aimed at detecting genetic regulation of gene expression in glaucoma-relevant eye tissues, we hope in the future, to provide a more complete understanding of POAG risk and IOP variation.”

Edited by Dawn Wilcox, BSN, RN and Miriam Kaplan, PhD

Source: Ryan Jaslow, Mass General Brigham, Medical Xpress, February 16, 2024; see source article