Richard K. Lee, M.D., Ph.D.

Research Overview

My laboratory focuses on the molecular, cellular, proteomic, and neurophysiologic basis of glaucoma in experimental and human models. Using cutting edge experimental techniques and technologies, my lab is identifying pathways important for the development of glaucoma and retinal nerve cell death. These molecular pathways represent important new targets for the development of neuroprotective strategies to prevent blindness associated with glaucoma.

Identification of Molecular Pathways Associated with the Development of Glaucoma
Our molecular analysis of the glaucomatous retina using gene array analysis is providing insight into the molecular pathways which induce retinal ganglion cell death. We are treating glaucomatous eyes with anti-glaucoma medications and laser treatments and performing molecular analysis with gene array analysis and proteomics to understand the molecular changes caused by glaucoma and retinal ganglion cell death. These molecular pathways which are differentially regulated in treated glaucomatous eyes relative to untreated, glaucomatous controls represent molecular targets for developing new and novel neuroprotective agents.

Using molecular pathway maps and differential gene expression analysis, we have identified molecules associated with inflammation, structural proteins, synaptic signaling, among other pathways which are associated with retinal ganglion cell death associated with elevated intraocular pressure. While we are studying these molecular pathways, we are also seeking to develop molecules that affect these pathways to develop neuroprotective treatments against the death of retinal ganglion cells.

Molecular Pathophysiology of Pseudoexfoliation Glaucoma
My laboratory is seeking to understand the molecular pathophysiology of pseudoexfoliation (PXE) glaucoma. PXE is characterized by PXE material, which is found throughout the human body and especially in the eye, which is the only known site of disease with glaucoma. PXE material has eluded identification since it was first characterized over a hundred years ago. Psueodoexfoliation material is being collected from patients with pseudoexfoliation glaucoma and we are determining the nature of the pseudoexfoliative material using proteomic approaches. By identifying and cloning the PXE material, genetic screening will be possible for this often occult form of glaucoma when it is in the early stages of disease with implications not only for the optic nerve but also during surgical procedures such as cataract extraction. The molecular characterization of PXE material will also allow for the development of directed anti-glaucoma therapy based upon the molecular nature of the PXE material.

Imaging Technologies for Assessing Glaucoma
Using the most advanced ocular imaging technologies, we are correlating structural features of the optic nerve and anterior segment of the eye with the development and presence of glaucoma. Our recent work with the Ocular Response Analyzer (ORA) seeks to understand how biomechanical properties of the eye may correlate with susceptibility to glaucoma. Using high resolution ultrasound biomicroscopy (UBM), we are studying the anterior segment structures of the eye and correlating these structures and the risk of developing glaucoma. UBM allows for fine resolution imaging of the angle and trabecular meshwork, which is where fluid drains from the front of the eye and regulates the intraocular pressure. We are also currently using conventional optical coherence tomography (OCT) and spectral domain OCT (SD-OCT), which is a much higher resolution form of OCT, to perform in vivo histology of the optic nerve to understand how these structural changes in the optic nerve may affect the risk for developing glaucoma. In addition, we are seeking to improve how SD-OCT is used to characterize and study the progression of glaucoma by measuring the nerve fiber layer thickness with OCT.

Histopathology of Glaucoma and Ocular Tumors
We are studying the histopathologic changes involved in eyes with prior glaucoma drainage implants. Using immunohistochemical techniques to assay known wound healing molecules, we are developing an understanding of how the eye responds to implanted material and how this wound healing response affects the efficacy of glaucoma drainage implants in regulating intraocular pressure. In addition, we are studying the molecular origins and markers for ocular tumors using immunostaining methods.