My laboratory is interested in understanding how endogenous and environmental factors influence the function of the retinal pigment epithelium (RPE) and contribute to the development and resolution of degenerative retinal diseases. Our research focuses on two main areas, diabetic retinal edema and age-related macular degeneration.

Retinal edema, the accumulation of fluid within the extracellular spaces of the neurosensory retina, is a common element in several retinal diseases and is a leading cause of vision loss in the Western countries. While the principle source of this extracellular fluid is considered to be leakage from blood vessels, our studies have demonstrated that alterations in RPE function also contribute to the development of retinal edema. Pathologic conditions, such as hyperglycemia or the accumulation of advanced glycation-end products in the vitreous fluid induce the secretion of cytokines. We have previously shown that these cytokines can alter the barrier function and secretory properties of the RPE. Our recent studies in vivo and in vitro provided new evidence that natriuretic peptides (NPs), hormones with diuretic and vasodilatory properties, have the ability to prevent the cytokine-induced breakdown of RPE fluid resorption and barrier function. Therefore, we expect that are likely to be a beneficial for edematous fluid and a convenient addition to the current limited spectrum of clinical treatment options.

Age-related macular degeneration (AMD) is responsible for most old-age visual loss in the United States. A potentially crucial factor in the development of AMD is the fluorescent lipofuscin, which accumulates with age in the lysosomal compartment of the RPE and primarily in the posterior pole of the eye. A principal component of lipofuscin is the vitamin-A by-product, A2E, which is toxic at high concentrations in cell culture models. However, due to a mismatch between the traditional methods of detection for lipofuscin (fluorescence) and A2E (bioanalytics), it has not been previously possible to directly correlate A2E with lipofuscin. Utilizing imaging mass spectrometry (MALDI-IMS), we have recently managed to bridge this gap and to determine the spatial distributions of A2E and lipofuscin in the human RPE. Our data provided convincing evidence that lipofuscin and A2E do not spatially correlate in the human eye (independent of AMD condition). Therefore, my laboratory is engaged in understanding the toxic component of lipofuscin, and the significance of A2E in the periphery. MALDI-IMS provides a unique opportunity to chemically identify relevant molecular information based on imaging modalities commonly used for clinical diagnosis (such as fluorescence).