Transcript Research Activities at DMEI

Research Activities at the Dean
McGee Eye Institute
Gregory Skuta, MD
Professor and Chairman, Department of Ophthalmology
President and CEO, Dean McGee Eye Institute
Robert Eugene Anderson, MD, PhD
Dean McGee Professor of Ophthalmology
George 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.
Nanoceria inhibit development
of leaky retinal vasculature
C
4X
4X
4X
C57
VLDLr + Saline
VLDLr + CeO2
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 Ophthalmology
Asst. Dean, Office of Postdoctoral Affairs
Neovascularization of the Cornea
Neovascularization in the Mouse
Epithelium
Uninfected
Limbus region and central
cornea demarcated by white
segmented line.
HSV-1
Red = blood vessel (CD31+)
Endothelium
Infected
•
Green = lymphatic vessel (LYVE1+)
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?
Techniques to answer question:
Cornea from Human Patient Diagnosed with bacterial keratitis with
blood and lymphatic vessels prominently displayed.
•Flow cytometry.
•Real time PCR.
•Confocal Microscopy
•Suspension Array Analysis
What Factors and Cells
Drive Neovascularization
in the Human Patient
Cornea?
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 eye
Michael H. Elliott, PhD
Caveolin-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. Retina:
Conventional outflow:
• Schlemm’s Canal (SC)
• Trabecular meshwork (TM)
Caveolin-1 has been linked to:
• autoimmune uveitis
Corneal epithelial stem
cell niche:
• diabetic retinopathy
• reduced retinal function
• blood-retinal barrier integrity
• corneal epithelial wound healing
•primary open angle glaucoma
Michael H. Elliott, PhD
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
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.