Research Activities at the Dean McGee Eye Institute

Gregory Skuta, MDProfessor and Chairman, Department of Ophthalmology

President and CEO, Dean McGee Eye Institute

Robert Eugene Anderson, MD, PhDDean McGee Professor of OphthalmologyGeorge Lynn Cross Research Professor

Director of Research

Research at the Dean McGee Eye Institute

• 7 independent researchers with funded laboratories

• 4 professors, 1 associate professor, and 2 assistant professors

• 9 graduate students, 6 postdoctoral fellows, 6 “junior” faculty

• Current research space- ~34,000 sq. ft.

• Current grant funding (DMEI)- ~$8M (year); ~$34M (total)

• Current grant funding (campus)- ~$17M (year); ~$70M (total)

• Five core modules that support the research effort• Live Animal Imaging (OCT, ERG, optomotor acuity, funduscopy,

tonometry, slit lamp)

• Cellular Imaging (confocal and epifluorescence microscopy, flow cytometry, cryosectioning, full histology service)

• Molecular Biology (Primarily genotyping)

• Lipidomics (GC/MS, LC/MS/MS)

• Vivarium (Renovated state-of-the-art facility for rodents and rabbits)

Ongoing Research at the Dean McGee Eye Institute

• Age-related macular degeneration (Anderson, McGinnis, and Mandal)

• Stargardt Disease (Anderson, Agbaga, and Mandal)

• Diabetic retinopathy (McGinnis, Elliott, and Rajala)

• Bacterial endophthalmitis (Callegan and Coburn)

• Viral eye infections (Carr)

• Ocular inflammation/Immunology (Carr, Callegan, Elliott, and Mandal)

• Retinitis pigmentosa (Anderson, Mandal, Wong, Cai, Rajala, and McGinnis)

• Blood retina barrier dynamics (Elliott)

• IOP regulation in glaucoma (Elliott)

• Corneal wound healing (Cohen and Elliott)

• Endogenous neuroprotective mechanisms (Rajala and Anderson)

• Multidrug Resistance (Callegan and Coburn)

Vacancy Engineered Cerium Oxide Nanoparticles

• James F. McGinnis, PhD

• Professor of Ophthalmology, Cell Biology, and Neuroscience

• University of Oklahoma Health Sciences Center

• Dean McGee Eye Institute

Cerium Oxide – CeO2

• Cerium oxide exists as a lattice crystal with oxygen vacancies.

• Cerium is a member of the Lanthanide Series of Rare Earth Elements.

4X

VLDLr + CeO2C57

4X

VLDLr + Saline

Nanoceria inhibit development of leaky retinal vasculature

C

4X

Mice with deletion of VLDL receptors grow new blood vessels in their retinas, which makes them an excellent model for studying neovascularization.

Daniel J.J. Carr, Ph.D.Presbyterian Health Foundation Presidential Professor

M.G. McCool Professor of OphthalmologyAsst. Dean, Office of Postdoctoral Affairs

Neovascularization of the Cornea

Epithelium

Endothelium

HSV-1

Uninfected

Infected

Neovascularization in the Mouse

Limbus region and central cornea demarcated by white segmented line.

Red = blood vessel (CD31+)

Green = lymphatic vessel (LYVE-1+)

• Herpes simplex virus type 1 (HSV-1) induces neovascularization in the mouse cornea.

• Lymphangiogenesis (genesis of lymphatic vessels) in the mouse cornea is unique driven by VEGF A via VEGFR2.

Neovascularization of the Cornea

QUESTION:

DOES THIS SAME PROCESS OCCUR IN HUMAN CORNEA AND WHAT IS THE MECHANISM?

Cornea from Human Patient Diagnosed with bacterial keratitis with blood and lymphatic vessels prominently displayed.

What Factors and Cells Drive Neovascularization in the Human Patient Cornea?

Techniques to answer question:

• Flow cytometry.

• Real time PCR.

• Confocal Microscopy

• Suspension Array Analysis

Michael H. Elliott, PhD

Assistant Professor of Ophthalmology

Adjunct Assistant Professor of Physiology

Research areas:

• Mechanisms that regulate blood-retinal barrier integrity

• Novel regulators of retinal inflammation

• Role of CAV1 in primary open angle glaucoma

• Corneal stem cells/wound healing (collaboration with Alex Cohen, MD, PhD)

Caveolin-1 in the eyeCaveolin-1 is the signature protein of membrane domains called caveolae

and is expressed in several cell types in the retina, aqueous outflow pathway, and cornea.

Michael H. Elliott, PhD

Conventional outflow:• Schlemm’s Canal (SC)• Trabecular meshwork (TM)

Retina:

Corneal epithelial stem cell niche:

Caveolin-1 has been linked to:• autoimmune uveitis• diabetic retinopathy• reduced retinal function• blood-retinal barrier integrity• corneal epithelial wound healing• primary open angle glaucoma

Potential resident research projects:

• Clinical evaluation of mouse models of blood-retinal barrier dysfunction and ocular inflammation:

Funduscopic examination Fluorescein angiography IOP measurements Slit lamp evaluation

• Culture and manipulation of human corneal epithelial stem cells

• Analysis of caveolin expression in ocular disease specimens: Diabetic retinopathy Primary open angle glaucoma Autoimmune uveitis Age-related macular degeneration

Michael H. Elliott, PhD

Summary

• Basic research into the causes and prevention of the major blinding and debilitating eye diseases is alive and well at the DMEI.

• Clinical research and clinical trials (not discussed here) are also major activities at DMEI.

• We have excellent facilities that support resident research projects.