Unveiling The Role Of Peroxiredoxin 6 in Maintaining Trabecular Meshwork Homeostasis

Progression of glaucoma appears to be related to overstimulation of certain genes that control the matrix surrounding cells in a part of the eye, called the Trabecular Meshwork (TM). This overstimulation occurs when TM cells face oxidative stress due to reduced levels of antioxidant(s). By supplying Peroxiredoxin 6, PRDX6, an antioxidant protein, we will be able to restore these over modulated genes by blocking oxidative stress-induced deleterious signaling.

Recent evidence implicates that the oxidative stress plays a role in cause and progression of various ocular diseases including glaucoma, and suggests that aged cells are prone to this damage due to diminished expression of antioxidants. The eye is constantly exposed to radiation, atmospheric oxygen and environmental chemicals, and these factors continuously generate free radicals. If not quenched, this increases local accumulation of free radicals in the cellular microenvironment and causes ocular cell damage that leads to pathological changes. Glaucoma is a major eye disease causing blindness. One of the most important events in glaucoma is the elevation of intraocular pressure, which is associated with the specialized cells of the eye, called trabecular meshwork (TM). These cells are responsible for maintaining normal intraocular pressure and any abnormality or damage to the cells results in the development of glaucoma. Using human TM cell as a model system, Dr. Fatma will discover the major factor(s) responsible for the initiation of disease process and she will document how the changes in expression level of peroxiredoxin (PRDX) 6, a multifunctional protective protein, influence the vulnerability of TM cells against oxidative stress, and document how reduced expression of PRDX6 in these cells, is one of the causes of TM cell damage/ abnormality that in turn yields to elevated intraocular pressure (IOP) and to glaucoma. In the extension of this project, she will reveal whether a delivery of PRDX6 could reverse these changes. Overall, successful completion of this project will have a significant impact toward the efforts in developing newer means of therapy for glaucoma that should in turn, reduce the economic burden and other complication as well as may be an asset for developing countries in treating or postponing glaucoma.

Progress Updates

One of the most important events in glaucoma, a major eye disease causing blindness, is the elevation of intraocular pressure which is associated with the specialized cells called trabecular meshwork (TM). These cells are responsible for maintaining normal intraocular pressure and any abnormality or damage to the cells resulting from the development of glaucoma. We found that Peroxiredoxin (PRDX) 6, a multifunctional protective protein, is highly expressed in normal TM cells, but its expression is significantly reduced in TM cells in eyes with glaucoma. We surmised that reduced expression of PRDX6 in glaucoma cells may be a cause of initiation of pathophysiology in TM cells. Importantly, we observed that TM cells from individuals with glaucoma show structural changes and abnormal expression of certain proteins. These abnormalities of TM cells could be reversed following external treatment with PRDX6. Our data is encouraging and may provide a base for future treatments/preventions of glaucoma.