Glaucomatous Damage Mechanisms: Axonal Cytoskeleton and Relation to Birefringence of Retina Nerve Fiber Layer

Project Summary

Glaucoma, a leading cause of blindness worldwide, damages a tissue in the eye called the retinal nerve fiber layer, or RNFL. To aid in diagnosis of glaucoma, doctors use optical instruments to image the RNFL, hoping to detect abnormalities before significant loss of vision. Our laboratory has studied the optical properties of normal RNFL for many years and has made a number of important discoveries. We now feel that we understand most of the optical properties of normal RNFL and we have some ideas about how these properties relate to the cellular structures inside nerve fibers. For example, we have shown that one clinically important property, called birefringence, is due to long, very thin filaments, called microtubules, that exist inside all nerve fibers. Microtubules are one component of the complex internal structure of nerve fibers. In spite of our progress with normal RNFL, we still know little about the changes in optical properties caused by glaucoma, nor do we understand the changes in cellular structure that enable us to detect abnormal RNFL in patients. In this project, therefore, we are tackling these important questions. Because change in RNFL structure precedes RNFL loss, detecting early structural change can open a window during which treatment might prevent or even reverse glaucomatous damage. We are pursuing three specific aims in this project. First, we will use special stains to label different internal components of the nerve fibers in the RNFL to learn how they are distributed at different stages of glaucoma. Second, we will compare these components, trying to learn which is most sensitive to damage. Third, we will look specifically at the relation between structural damage, particularly damage to microtubules, and changes in RNFL birefringence. A unique feature of our research is that the studied structures relate directly to clinically-detectable properties of the RNFL. Thus, we expect the results to lead directly to improved sensitivity for RNFL damage in clinical testing of patients.