Location: Cleveland Clinic Main Campus
Research and Innovations:
Age-related macular degeneration (AMD) etiology is complex, and we know that it includes both a genetic component and environmental risk, the strongest being advanced age. As the retina and retinal pigment epithelium (RPE) ages, many structural and physiological changes occur. Although these changes are well known, the underlying mechanisms involved in them are frequently poorly understood. It is also important to dissect the changes due to aging from the ones due to pathology. My long-term goal is to understand how age-related macular degeneration (AMD) pathology affects RPE cellular function. To this end, my research is focusing on aging and oxidative stress function, an etiological driver of RPE degeneration in AMD pathology. Specifically, we are investigating the antioxidant mechanisms regulated by DJ-1. DJ-1 is a multifunctional protein that plays an essential role in the oxidative stress response in neurodegenerative disorders such as familial and sporadic PD, amyotrophic lateral sclerosis, Alzheimer, and Huntington’s disease. My work has demonstrated that the aging DJ-1 KO mice display degeneration of retina and RPE cells, changes in mitochondria structure and function, and increased inflammation, all hallmarks of AMD. We hypothesize that limiting the formation of reactive oxygen species within the RPE may effectively prevent or reduce RPE dysfunction observed in AMD patients. In this context, my lab will analyze RPE antioxidant and mitochondrial functions regulated by DJ-1. I also intend to test the therapeutic potential of DJ-1 in animal models that recapitulate features of AMD. My lab looks to model AMD by superimposing additional etiological drivers (e.g. inflammation, cigarette smoking, light exposure) to our animal model. Finally, my lab aims to perform ex-vivo imaging, histology, Immunohistology and of eyes from donor with AMD. The aim of this research is to correlate morphological and molecular signatures of RPE/photoreceptors degeneration with ex-vivo imaging findings. The crosstalk study between RPE degeneration, mitochondrial function, oxidative stress, autophagy and DJ-1 function is novel and has translational potential.