Zsolt Ablonczy, Ph.D.
SUMMARY OF LABORATORY RESEARCH
The retinal pigment epithelium is a single layer of tightly connected cells between the photoreceptors and the choroidal blood supply. The primary function of the retinal pigment epithelium is to provide the photoreceptors with nutrients necessary for their survival and proper function. The retinal pigment epithelium also removes any harmful waste products generated within the retina. In addition, the RPE is responsible for keeping the outer retina dry, which is essential for high visual acuity. 20/20 vision is not possible without a healthy retinal pigment epithelium and the functional deficiency of this tissue is a common element in several retinal diseases (dry- and wet-AMD, retinitis pigmentosa, diabetic retinopathy, macular edema, retinopathy of prematurity, etc.). While most of these devastating diseases are considered to be multifactorial, the underlying reasons are still not clear. The main interest of my laboratory is to understand how endogenous and environmental factors influence the function of the retinal pigment epithelium and contribute to the development of retina degeneration. To understand these processes, my laboratory is currently involved in two major research projects.
The first project is focusing on the barrier function of the retinal pigment epithelium. The barrier function of the retinal pigment epithelium is ultimately responsible for the tight connection between the cells; however, it also determines the structural makeup of the cells, involving orientation and polarization as well as influencing the cellular metabolic pathways. Within this project we utilize cutting-edge medical diagnostic tools, such as the high resolution Heidelberg Spectralis Optical Coherence Tomograph, to understand the development and resolution of retinal edema, a major cause of loss of visual acuity in wet AMD, diabetic retinopathy, and following eye injuries or surgeries. We have recently discovered a new protective mechanism, based on the activities of protease enzymes, which is capable of protecting against the accumulation of edematous fluid by regulating the receptors of inflammatory cytokines. Currently we are working on understanding how to use the different pieces of these receptors released by the proteases to pharmacologically promote the reabsorption of edemas and the recovery of lost barrier function.
The second project is interested in the development of dry macular degeneration. It has long been recognized that the development of dry macular degeneration depends on the activity of the normal visual cycle between the photoreceptors and the retinal pigment epithelium. The visual cycle is based on the biochemical transformations of retinoids, which are highly reactive molecules, and especially sensitive to the high light environment of the photoreceptors. These processes allow the generation of abnormal retinoid photoproducts, which accumulate in the retinal pigment epithelium and are thought to be responsible for its functional degeneration and eventual vision loss. We have recently developed a new, mass spectrometry-based molecular imaging technology, which is capable of spatially detecting and following the specific biochemical transformations of these retinoid side-products. The surprising discovery of these experiments was that the retinoid metabolism is segregated between the central and peripheral eye. Currently we are working on understanding the molecular mechanisms of why the retinoid side-products are metabolized differently depending on the geographical area of the human eye.