Biophysical Cues, Antioxidants and Trabecular Meshwork

Summary

The capacity of trabecular meshwork cells to resist oxidative stress is reduced in glaucoma. Research to investigate this loss in protection of the cells has disregarded the importance of biophysical cues in contributing to the antioxidant status. This study examines the contribution of nanoscale surface features and biomechanics to the total antioxidant status of these cells.

Project Details

Summary

Trabecular meshwork cells are responsible for controlling intraocular pressure. Oxidative damage has recently been shown to be a factor in glaucoma. The proposed research will investigate how these cells are affected by the physical properties of the surface on which they are grown in terms of their ability to prepare for, and respond to, oxidative stress (i.e., free radical damage). We will determine both the "at-rest" antioxidant status of these cells, as well as how varying physical cues affect the response of trabecular meshwork cells to oxidative stress.

Specific aims

• Biophysical cues affect antioxidant status of trabecular meshwork cells. We will grow trabecular meshwork cells on surfaces with a variety of patterns (in the submicron to nanoscale range) and stiffnesses, mimicking that of the normal and glaucomatous states. We will determine the levels of antioxidant protection, as well as levels of oxidative damage to the DNA of the cells.
• Biophysical cues improve the ability of trabecular meshwork cells to recover from oxidant stress. Using similar surfaces, we will apply oxidative stress to trabecular meshwork cells, and compare the recovery of the cells to those grown on conventional surfaces.

Benefit to public

Glaucoma is a devastating and blinding disease, estimated to affect almost 80 million people by 2020. Much remains unknown about its initiation and progression, and current treatments are limited. We have discovered numerous relevant effects of surface physical properties on trabecular meshwork cells, including antioxidant status, and there is mounting evidence that oxidative damage is involved in glaucoma. This research will contribute significantly to the overall understanding of the mechanisms of glaucoma, which may eventually facilitate the development of new therapies.

Innovation

The vast majority of cell culture research is carried out using rigid surfaces that do not approximate the environment that the cells would experience in the body. To our knowledge, we are the only laboratory using biologically relevant surfaces in the submicron to nanoscale range to study human trabecular meshwork cells. Our previous studies have demonstrated numerous effects of surface characteristics on these cells in both health and disease, and this is the first study that would investigate the effect on antioxidant status.