The Kleinman Laboratory for Ocular Biology and Imaging

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Established in 2012 at the University of Kentucky

Mark Kleinman, MD, Principal Investigator, Ocular Biology & Imaging Lab, Department of Ophthalmology, University of Kentucky College of Medicine
Mark Kleinman, MD, Principal Investigator

We are a team of scientists with expertise in different fields of biology, united by our common interest in the biology of vision. Mark Kleinman, MD, a vitreoretinal surgeon with a long-standing commitment and expertise in biomedical research, is the Principal Investigator of our studies. We are intensely focused on two significant aims that harness the potential to change the way we visualize and treat retinal diseases.

How does aging lead to retinal cell death?

Our long-term goal is to identify new signaling pathways that serve as master switches for aging and inflammation

Although great strides have been made in vitreoretinal biology and medicine, the molecular underpinnings of dry age-related macular degeneration (AMD) and death of the retinal pigment epithelium (RPE) remain elusive. Our long-term goal is to identify new signaling pathways that serve as master switches for aging and inflammation in the RPE to target for both diagnostic and therapeutic benefits in patients with dry AMD.

Gene expression map
Gene Expression Patterns of the Aging Acetylome

To scientifically investigate this complex biology, we are using a multi-pronged approach to dissect the underlying disease mechanisms. Beginning at the epigenome, we are investigating a library of epigenetic molecules called histone deacetylases (HDACs) for their contribution to inflammation and RPE cell death. In the course of our study, we have identified specific HDACs that lead to an intense inflammatory phenotype resulting in RPE degeneration. Utilizing advanced, next-generation techniques in molecular biology, including massively parallel sequencing and mass-spectrometry, we are dissecting the interacting partners and signaling cascades initiated by these critical regulatory factors. These studies will shed much-needed light on the pathogenesis of AMD.

Secondly, we are trying to understand the inflammatory landscape that accompanies RPE cell death. With systems biology and transcriptomics, we have identified a specific pro-inflammatory gene expression profile that is highly correlated with this disease and are actively pursuing techniques to suppress these pathways for the treatment of dry AMD.

Imaging the Unimaginable

Another major problem that plagues many aging diseases of the retina is that by the time a patient visits the doctor with reduced vision, the disease is already too advanced and therapy can be aimed only toward preserving what little function remains. Addressing this dilemma is a critical goal for our lab.

Inflammasome Imaging
Inflammasome Bio-Imaging in the RPE

We are currently developing novel approaches to peer into the eye using non-invasive techniques in molecular imaging to identify diseased cells prior to signs of permanent anatomic changes or loss of vision. We have pioneered the use fluorescent probes that bind to caspases, a class of proteases that are activated during the cell death process, for intraocular use to detect RPE cell death in vivo.

We are currently developing novel approaches to peer into the eye using non-invasive techniques

In multiple collaborations, we are also simultaneously studying the efficacy of similar probes that bind other molecules critical to the degenerative and early pathogenetic processes. Our library of bio-probes are engineered to detect an array of different targets and fluoresce once bound. Localization of the probe is performed using conventional imaging equipment in an ophthalmologist’s office without the need for invasive procedures or biopsy. Once validated, these probes could detect a wide range of ocular diseases earlier than is currently possible via routine eye exams, thus enabling earlier treatments and better preservation of vision for patients.