National Glaucoma Research - Current Award

	XiangRun Huang, Ph.D. Bascom Palmer Eye Institute Miami, FL Title: Glaucomatous Damage Mechanisms: Axonal Cytoskeleton and Relation to Birefringence of Retina Nerve Fiber Layer Non-Technical Title: How are Cellular Structures in Retinal Axons Damaged in Glaucoma? Acknowledgements: Recipient of the Dr. Douglas H. Johnson award for glaucoma research. Duration: April 1, 2008 - March 31, 2011 Award Type: Standard Award Amount: $100,000
Summary: Little is known about the changes in optical properties caused by glaucoma, nor is it understood what changes in cellular structure might enable detection of abnormal tissue in patients. This study seeks to enhance this knowledge. Since change in the retinal nerve fiber layer (RNFL) structure precedes RNFL loss, detecting early structural change could facilitate treatment to prevent or even reverse glaucomatous damage. The study may also lead to improved sensitivity for RNFL damage in clinical testing of patients.

Details:

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.

Publications:

Huang, X.-R., and Knighton, R.W.: Altered F-actin distribution in retinal nerve fiber layer of a rat model of glaucoma. Expt. Eye. Res., 88: 1107-1114, 2009 (PMID: 19450448)[link not available] This study reports patterns of change in a cellular structure in an eye tissue damaged by glaucoma. The result helps to understand damage mechanisms of glaucoma. Kong, W., Huang, X.-R. and Zhou, Y.: Distortion of Axonal Cytoskeleton in Glaucomatous Retina. Inves. Ophthalmol. Vis. Sci., ARVO E-Abstract#2119, 2010. The study reports altered distribution of cellular structures in an eye tissue with glaucomatous damage. Understanding which structures are damaged first in the disease will help to improve sensitivity for clinical detection of glaucoma.