Download (one of two NIH P30 grants at the OUHSC).

The Visual System: Opportunities for
Collaborative Research
Robert Eugene Anderson, MD, PhD
Departments of Ophthalmology and Cell Biology
University of Oklahoma Health Sciences Center
Dean McGee Eye Institute
March 24, 2017
Vision Research at the OUHSC
•
19 independent vision researchers with appointments in the Departments of
Ophthalmology, Cell Biology, Physiology, Medicine, and Geriatrics in the COM and the
Department of Pharmaceutical Sciences in the COP.
•
NEI P30 Vision Center grant (one of two NIH P30 grants at the OUHSC).
•
NEI T32 Vision Training grant (one of two NIH T32 grants on campus).
•
Research support- $40M from federal, industry, local/state, and foundations.
•
Vision grants from the National Eye Institute are exceeded only by grants from the
National Cancer Institute.
•
Core modules support the research effort
•
DMEI Vivarium (Renovated state-of-the-art facility for rodents)
•
Live Animal Imaging Core (OCT, ERG, optokinetics/acuity, funduscopy, tonometry,
biomicroscopy/videography) located in the DMEI and BMSB vivaria
•
Cellular Imaging Core (confocal and epifluorescence microscopy, cryosectioning, full histology
service) located at the DMEI
•
Molecular Biology (Primarily genotyping) located at the DMEI
The Visual System
The Visual System
What can go wrong with the visual system and what can we
do about it? Where do we need more help from technology?
Drug-delivering contact lenses to test efficacy of
antibiotic peptide in animal models of bacterial keratitis
• Advantages of using contact lenses vs
eye drops: sustained delivery.
• This is particularly important in the case of
corneal infection because eye drops have to be
applied every hour at the beginning of
treatment.
•
Dr. Anne Pereira’s laboratory is developing a
peptide derived from the cationic antimicrobial
protein CAP37 for the treatment of corneal
infections that are resistant to classical
antibiotic treatments.
The use of drug-eluting contact lenses would be useful to test the efficacy of the peptide
in animal models and would be beneficial for clinical use in patients.
H. Anne Pereira, PhD
Dept. Pharmaceutical Sciences, COP
[email protected]
Anne Kasus-Jacobi, PhD
Dept. Pharmaceutical Sciences, COP
[email protected]
Fundus photographs and fluorescein angiograms of
diabetic retinopathy
Breakdown of RPE barrier in diabetes
Diabetic cystoid macular edema
De novo leakage in diabetic mice
Fluid accumulation in subretinal gaps and
exudative retinal detachment in 30% patients
of diabetic macular edema, major vision loss
in diabetic retinopathy
Retinal section
OCT imaging
20kDa FITC-dextran
RPE
RPE barrier-specific leakage
Ozdemir H. et al. Acta Ophthal. Scandi.(2005)
83:63
Project- Dr. Le’s lab studies diabetes-induced leakage from the choroidal vasculature, the vessels
beneath the retinal pigment epithelium (RPE), which are responsible for approximately 80 percent of
the retinal blood circulation (red arrows).
Problem- There is no non-invasive quantitative assay to measure RPE barrier leakage in live animals.
Additional complication- Experimental animals develop cataracts after 2-3 months of diabetes.
Yun-Zheng Le, PhD
Departments of Medicine and Physiology, COM
[email protected]
Making a better rodent diabetes model
Background
• All Type I and many Type II
diabetics take insulin
• Human insulin administration
has moved to implanted
pump systems
• Closed loop systems –
continuous glucose
monitoring and insulin
delivery are the future
Challenge
• Making animal models match the
human patients for preclinical studies
• Current rodent systems for insulin
administration are simplistic:
• Limited lifespan
• Continuous administration
• No monitoring
Need
• Controllable, long lasting insulin
pump systems for rodents
• Develop advanced rodent models for
preclinical biology and drug
development studies.
Bill Freeman, PhD
Depts Physiology and Geriatric Medicine, COM
[email protected]
Project- Dr. Elliott studies vascular dysfunction in the aging retina.
Problem- There are no appropriate modalities to measure in vivo retinal blood flow in rodent models of vascular dysfunction.
Collaboration with biomedical engineers at OU with significant expertise in quantitative, in vivo blood flow measurements would
allow him to either enable current technologies (e.g., optical coherence tomography with Doppler) or develop new ones to
enhance his research capabilities and make his studies more competitive for extramural funding.
Michael Elliott, PhD
Department of Ophthalmology, COM
[email protected]
Objective Determination of Treatment
Points for Retinopathy of Prematurity
currently a subjective assessment of
fundus exam
--objective endpoints are needed for
telemedicine and disease management in
rural and less developed areas
1. Ability to digitally quantitate vessel
dilation and tortuosity to assign a
numerical definition of plus disease
2. Ability to measure vascular growth to
different zones in the retina (1-2-3)
3. Ability to detect extraretinal
neovascularization (stage 3 disease)
https://www.google.com/#q=Images+of+retinopathy+of+prematurity&*
R. Michael Siatkowski, MD
Dept. Ophthalmology, COM
Dean McGee Eye Institute
[email protected]
2D and 3D Culture Matrices that Support Survival, Growth, and
Synapse Regeneration by Mature Photoreceptors


Synapses between horizontal neurons (H,
green) and rod and cone photoreceptors
(small and large boxes, respectively).

Degenerative retinal diseases cause loss of rod
and cone photoreceptors and disrupt their
complex synaptic connections, causing
blindness. To restore sight, photoreceptors
must be replaced and regenerate these
connections. However, they do so poorly.
No good models to study photoreceptor
synapse regeneration exist currently. We need
2D and 3D cell culture matrices that support
survival, growth, and synapse regeneration by
rod and cone photoreceptors and other retinal
neurons to visualize the process of synapse
regeneration and identify the key mechanisms
that regulate it.
These advances in our knowledge will be
critical to developing therapies to restore sight.
David Sherry, PhD
Department of Cell Biology, COM
[email protected]
Other opportunities for collaborations
Michelle Callegan, PhD, Department of Ophthalmology, COM. The Callegan Lab studies the therapeutics and pathogenic
mechanisms of bacterial eye infections. Because these infections can quickly cause vision loss, delivery of high and
sustained drug concentrations is paramount to improving visual outcomes. There is a need for better drug delivery
systems that 1) sustain drugs at the ocular surface, 2) facilitate penetration into deeper tissues the eye from the surface,
and 3) sustain adequate levels inside the eye. Collaborating on nano-drug delivery or contact lens-sustained drug
delivery would likely make our projects more attractive for extramural funding. [email protected]
Dimitrios Karamichos, PhD, Departments of Ophthalmology and Cell Biology, COM. Our new team seeks to develop a
novel 3D bio-printing method to create the first human corneal endothelium tissue. Results from this work will pave
the road for developing biological substitutes for damaged endothelium, which lacks the intrinsic regenerative capability.
[email protected]
Scott Plafker, PhD, Oklahoma Medical Research Foundation. Our research efforts could be greatly advanced if we could
track the subcellular localization of proteins and organelles in the RPE cells of live mice expressing fluorescent
markers. One particular challenge with this is the high level of autofluorescence of these cells. Software and high
resolution microscopy to overcome this barrier would represent a major step forward to our research program. [email protected].
Xi-Qin Ding, Ph.D., Department of Cell Biology, COM. One of the exciting projects in my laboratory is to determine the
potential of photoreceptor protection by suppressing thyroid hormone signaling locally in the retina. Our ongoing efforts
focus on topical delivery of thyroid hormone suppressants by eye drops. We anticipate a potential collaboration with
faculty at SBME in nano-biomedicine area for optimization of the nanoparticle-mediated delivery of the therapeutic
agents and enhancement of the overall drug delivery bioavailability. [email protected].
Raju VS Rajala, PhD- Departments of Ophthalmology and Physiology, COM. We are currently collaborating with Dr.
Chuanbin Mao,Department of Chemistry and Biochemistry, University of Oklahoma, Norman, in the formulation of
magnetic/silica nanoclusters for eye gene therapy. These particles can be guided externally with a magnet to specific
locations in the eye. . [email protected]
What can go wrong with the visual system and what can we
do about it? Where do we need more help from technology?