Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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?