Sadun Lab





Lab News



The eye is brain. Our lab, officially designated as the laboratory of optic nerve studies, seeks to understand the human brain through the eye. The eye is highly accessible, psychophysically, through a variety of tests of visual function, in-vivo, through new imaging modalities such as Optical Coherence Tomography (OCT), and in-vitro, from post-mortem histopathological studies. In each case, the remarkable structural organization of the retina in regards to spatial and functional relationships, allow for precise understandings of structure and function. Taking advantage of this accessibility of the eye, we have investigated a number of diseases and degenerations of the central nervous system. In particular, we were the first to describe the visual and ocular changes of Alzheimer’s Disease (AD) beginning with a seminal article published in the New England Journal of Medicine in 1986. We have continued to explore the nature of inflammation and the intermediate inflammatory markers in the human retina.

Recently, we demonstrated with immunohistopathology, the presence of Amyloid-beta and pTau in the retinas of patients with AD. We have studied another disease that specifically targets one subclass of retinal ganglion cells (RGCs) and does so in young and otherwise healthy adults in a massive wave of degeneration over a period of only a few weeks leading to devastating bilateral blindness. This disease, Leber’s Hereditary Optic Neuropath (LHON) is carried by a mutation in a mitochondrial gene and hence is only passed by the mother. We have used LHON as a prototype of mitochondrial diseases to learn how mitochondrial impairment causes a variety of devastating brain and muscle degenerations. Using a variety of genetic, immunopathological, cybrid, histochemical, computational biology, and clinical techniques, we are seeking to understand how the mutation impairs electron transport and causes the accumulation of reactive oxygen species (ROS). These multidisciplinary studies have led us to believe it is in this abnormal accumulation of ROS that RGCs die and thus lead to blindness. And from this, we believe we will gain understanding of other brain diseases that are also caused by ROS.