CBR member Ken Mitton, of the Eye Research Institute, has been awarded a grant from the National Eye Institute, one of the National Institutes of Health.
His award (R15EY025089) is to study VEGF’s longitudinal effect on the retina and retinal vasculature in vivo. The award is for three years and $448,500. The grant application was reviewed in the neuroscience pool of R15 applications, and in addition to pursuing basic science questions the project involves students, especially undergraduate students, in the research effort.
The research training of Oakland University undergraduate students is a strength of the Eye Research Institute. ERI faculty focus on one-on-one research mentoring of OU bioscience students who are taking independent research credit or who are working on an Honors College thesis. In addition, ERI faculty provide basic science lectures for ophthalmology resident grand rounds in the Beaumont Health System, and mentor graduate students, post-docs, visiting vision science fellows from around the globe (for example, China, Brazil, and the UK), and medical students doing capstone projects.
What is the relevance of this award to public health?
Mitton writes that an increased concentration of vascular endothelial growth factor A-165 (VEGFA-165) causes the growth of leaky new blood vessels in retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. A related molecule called VEGFA-165b is considered a possible therapy to counter VEGFA-165's growth effects. However, Mitton hypothesizes that VEGFA-165b causes already-formed vessels to leak, and he has developed a rat-based model and cell-culture model to test this hypothesis.
His data to date indicate that the so-called b-isoforms of VEGFA can disrupt the blood-retinal barrier, similar to the regular VEGFA isoforms. Differences in signal transduction activation potential are being studied in human retinal endothelial cells, obtained from the retinas of donor eyes. Retinal endothelial cells line the inside of blood vessels and form the first part of the blood-retinal barrier. In addition to advanced training in gene expression and biochemical analysis, OU undergraduate students use noninvasive imaging methods to study rodent models, including retinal imaging, fluorescein angiography, and spectral domain optical coherence tomography. These methods monitor of the effects of VEGFA on the retinal vasculature over time in the same eyes of the same animals, and are used by the retinal services in ophthalmology clinics.
Mitton was inducted into the 2014 class of silver fellows of the Association for Vision and Research in Ophthalmology (FARVO) for his participation in vision science research, scholarship and service. He directs the live animal imaging and electroretinography services for the Pediatric Retinal Research Lab of the ERI, new skills he added several years ago to previous expertise in the control of gene expression and analytical biochemistry. He also directs the Summer Undergraduate Program in Eye Research (SUPER), which reviewers of his R15 proposal considered a particular strength because of SUPER’s track record of alumni who have entered prestigious graduate and medical school programs or are in ophthalmology resident training programs. The SUPER program is currently taking applications for this summer; the deadline for applying is March 1.
The Pediatric Retinal Research Lab was funded by the Vision Research ROPARD Foundation, supported by private donors. Since 2012 the PRRL has been a unique venue for PhDs and MDs to work together on translational research projects, including basic scientists collaborating with clinicians to develop new therapeutic drugs. Mitton sees this as a new frontier for bioscience research at Oakland University. Such collaborations will be another benefit from this NIH grant, which synergizes with the therapeutic development expertise of the research team in the PRRL.