Backed by a $1.16 million grant from the National Institutes of Health, UMKC School of Medicine vision researcher Peter Koulen, Ph.D., is studying new chemical compounds to treat and prevent age-related macular degeneration (AMD).
AMD is the leading cause of irreversible vision loss and blindness among older adults. As many as 11 million people in the United States have some form of age-related macular degeneration.
“AMD affects a significant and increasing portion of the U.S. population, with age being a predisposing factor,” said Koulen, director of basic research at UMKC’s Vision Research Center. “This research will contribute to improving health care and the prevention of blindness.”
His project, funded by the NIH National Eye Institute, will focus on the preclinical development of novel antioxidants that have the potential to be both preventative and therapeutic in nature. The compounds could prevent the deterioration and death of retina nerve cells and supporting cells. The retina cannot regenerate these cells, therefore, their loss as a result of AMD leads to irreversible damage to one’s vision.
If successful, these new antioxidants being developed by Koulen’s research would be effective in both preventing the disease from progressing and treating already existing damage.
The research focuses on dry AMD, a form of the disease that affects the majority of patients. Effective therapies are lacking for this form of the disease, in which cells are gradually lost over time resulting in blindness.
Medications developed as a result of the study could also complement existing treatment designs for the wet form of AMD that is more aggressive and affects a smaller number of patients.
Surgeons world-wide currently perform more than 240,000 corneal transplants a year to address a wide range of eye diseases. Researchers and physicians, however, estimate as many as 10 million patients could benefit from the procedure if enough viable tissue was available.
The University of Missouri-Kansas City Vision Research Center is part of a $1.5-million National Institutes of Health grant-funded project exploring the capability of a novel, ultra-fast technique of cryopreservation that could help meet those far-reaching clinical needs in ophthalmology and a number of other fields of medicine.
The NIH awarded a phase II Small Business Innovation Research (SBIR) grant to CryoCrate, a Columbia, Missouri-based company active in biomedicine working with the University of Missouri-Kansas City Vision Research Center. The new two-year award is for $1,566,168 and includes a subcontract of $722,870 to UMKC’s Vision Research Center. It is a follow-up grant to previous phase I SBIR funding from the NIH for earlier collaborative work between CyroCrate and UMKC.
With current techniques, many types of cells and tissues, including cornea tissues, cannot be preserved at all or lose their function when subjected to the freeze-thaw process of cryopreservation. Peter Koulen, Ph.D., professor of ophthalmology, endowed chair in vision research at the UMKC School of Medicine and director of basic research at the UMKC Vision Research Center, and Xu Han, Ph.D., president and Chief Technology Officer of CryoCrate, jointly developed a new cryopreservation technique to preserve the viability and functionality of cornea and bioartificial ocular tissues. The new phase II SBIR funding will allow Han and Koulen to extensively test and refine the technology before taking it to the clinics.
Thus far, traditional methods of cryopreservation have been unsuccessful to preserve and store human corneas for use in patients due to the fact that cells critical for cornea function are lost during freezing. Corneas need adequate numbers of such cells to be present and properly functioning in the grafted tissue for the surgery to be successful. This currently limits storage of corneas to refrigeration, which is insufficient in delaying the deterioration of cornea tissue beyond a few days and creates numerous clinical challenges shared by other areas of transplantation.
CryoCrate is headquartered at the Missouri Innovation Center. It commercializes a new cooling method that better preserves tissue in a frozen state with only negligible mechanical damage to the tissue. The technology is co-developed and co-owned by CryoCrate and UMKC. It also eliminates the need for so called cryoprotectants, chemicals that facilitate successful recovery of live tissue from freezing, but pose a range of medical and regulatory challenges. International patents pending and patents by CryoCrate and UMKC protect the technology and will enable CryoCrate and Koulen’s team at UMKC to address the urgent worldwide clinical needs and rapidly evolving fields of transplantation medicine.
The new NIH SBIR phase II grant allows Han and Koulen to further develop an upgraded system that is equally effective in the cryopreservation of whole corneas and large bioartificial tissue. This would enable long-term storage of the tissues and could make them more readily available when and where needed for clinical use and research.
Early tests at the UMKC Vision Research Center detected no statistical difference in the number and quality of the cells that determine cornea health and function, when comparing corneas cryopreserved using the new technology with fresh cornea tissue. This level of efficiency in preserving corneal tissue has not been achieved previously with traditional corneal cryopreservation techniques.
If further tests prove to be equally effective, the goal is to introduce the new cryopreservation products for clinical use in patients following completion of the new NIH SBIR phase II grant and subsequent regulatory steps of product development.
A diagnostic process used in routine eye exams could hold a key to early stage detection and long-term monitoring of subclinical and clinical traumatic brain injury.
The Leonard Wood Institute awarded a $383,837 grant to the UMKC School of Medicine to explore the use of microperimetry to detect changes in visual function that are the result of traumatic brain injury. The project’s principal investigator is Peter Koulen, Ph.D., director of basic research at the UMKC School of Medicine’s Vision Research Center in the Department of Ophthalmology.
Microperimetry measures the light sensitivity of the central retina. It is currently used in ophthalmology to identify damage to the retina and vision loss due to eye diseases.
“We’re not looking for treatments for traumatic brain injury. We’re looking for a quantitative method to detect the disease that tells the patient, your disease severity is a 9 out of 10 or a 2 out of 10,” Koulen said. “Being able to quantify the disease will help physicians to better evaluate their patients. And then, when there is a treatment, it will help evaluate the treatment as well.”
Interventions to prevent or stop traumatic brain injuries are most effective early in the disease, but are not possible without reliable and easily repeatable early stage identification and diagnosis.
Current tests to conclusively show subclinical, or non-recognizable, forms of traumatic brain injury and the degree of acute and long-term damage are typically costly and often imprecise without accurate baseline data.
Using the microperimetry technology, Koulen’s research will sample mild to moderately concussed patients, subclinical traumatic brain injury and non-concussed patients to achieve a baseline. That data will then be used to create a defined number of quantitative parameters and produce a specific fingerprint of functional changes in vision that allow the researcher to optimally perform early stage detection, grading and long-term monitoring of subclinical and clinical traumatic brain injury.
Koulen said the UMKC School of Medicine’s Department of Ophthalmology and its Vision Research Center are uniquely positioned to conduct research on the new diagnostic technique because their faculty includes nationally recognized experts in the retina and neuro-ophthalmology sub-specialties.
If successful, the technology will ultimately enable diagnosis without invasive or subjective measures and will likely also enable an assessment of the severity and long-term impairment resulting from traumatic brain injury.
“Our technology will address this urgent clinical need,” Koulen said.
Colleagues who knew Larry Piebenga, MD, speak of him with true regard as both a mentor and role model for medical research, education and patient care. A legendary ophthalmologist and teacher at UMKC, Piebenga was a pioneer for developing cornea and cataract therapies.
“Many of the ophthalmology techniques used today were first developed and implemented in clinics by Dr. Piebenga,” says Peter Koulen, PhD, UMKC professor and the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research. “Our faculty members still try to emulate him.”
“Dr. Piebenga was my mentor during my residency at UMKC,” says Timothy Walline, MD, assistant professor in UMKC’s Department of Ophthalmology. “His calm, caring manner inspired me then, and not a week goes by that I don’t fondly recall something he taught me. His sincere approach to each and every patient has been my guidepost in 25 years of practice and academic endeavors.”
“He always did the right thing no matter what the work involved was and cared for every patient no matter who they were,” says Abraham Poulose MD, FACS, associate professor in UMKC’s Department of Ophthalmology. “I have aspired to live my life, both personally and professionally, to the example that he set.”
In memory of Piebenga, his family has made a contribution to the UMKC Foundation to support a research study on corneal calcification, led by Koulen. The basic science study hopes to find ways of more precisely assessing corneal calcification and determining how changes that occur from the condition affect the ability to accurately diagnose eye diseases.
“This is potentially a high-impact study that affects the outcome of many patients,” says Koulen. “By properly diagnosing their condition, we can work to develop new therapies for eye diseases that affect patients’ vision.”
Koulen said he is excited that Piebenga’s family is making this gift to honor his legacy and hopes it inspires others to honor their loved ones with similar tributes.
“Dr. Piebenga was a true advocate of research funding and he put that commitment into action,” says Koulen. “As an avid philanthropist, he supported vision research at the UMKC Foundation, and the family’s gift showcases the mindset of Dr. Piebenga – that research is essential to our mission.”
He says their contribution also fills a critical gap for research funding as public funds are very competitive and are dwindling. “Donor gifts for small, initial studies such as this can lead to major funding for larger studies down the road,” he says.
“Research hinges on new discoveries, and philanthropy is a critical key in this process.”
Karl E. Kador, Ph.D., a researcher at the UMKC Vision Research Center, has received a nearly $2-million grant from the National Eye Institute at the National Institutes of Health. The funding will support his work to develop a novel approach for treating patients suffering end-stage glaucoma.
This most advanced phase of glaucoma is an extremely serious condition in which very little healthy retinal tissue remains. This results in a high level of visual damage and a much greater risk of blindness.
Kador’s research focuses on injuries and diseases of the optic nerve that lead to the death of retinal ganglion cells, which connect the retina to the brain. He is using tissue engineering to develop methods of transplanting new cells to replace those dead cells. The aim is to restore vision to patients suffering end-stage glaucoma and other eye disorders.
Kador’s NIH grant will be fully funded at $1,937,500 for a five-year period beginning May 1, 2018.
“The NIH R01 grant is widely considered the gold standard for outstanding biomedical research,” said Peter Koulen, Ph.D., Felix and Carmen Sabates Missouri Endowed Chair in Vision Research and co-director of the Vision Research Center. “Dr. Kador’s grant adds significantly to the national recognition and growth of our ongoing research programs at UMKC School of Medicine’s Department of Ophthalmology and Vision Research Center. These programs have been continually NIH-funded since 2009.”
An assistant professor of ophthalmology and biomedical sciences, Kador joined the School of Medicine and the Vision Research Center last March. Koulen said receiving this major NIH funding is an outstanding achievement in light of the difficult funding climate for researchers. He also noted that the grant comes less than a year after Kador joined the UMKC research faculty.
“Dr. Kador’s program, recognized by this highly competitive NIH support, brings the promise for groundbreaking and highly impactful research to Kansas City,” Koulen said. “But also, and more importantly, it brings renewed hope for our patients and the communities we serve.”
Nelson Sabates, M.D., chair of the UMKC Department of Ophthalmology and founder of the Vision Research Center, said there is an urgent need for enhanced research such as Kador’s to battle the adverse effects of glaucoma and similar eye diseases.
“A significant number of people suffer from glaucoma and other debilitating eye diseases such as age-related macular degeneration and diabetic retinopathy,” Sabates said. “Dr. Kador and his efforts in tissue engineering are another example of the novel work taking place at the Vision Research Center that will benefit individuals in our community and worldwide.”
The program at the Vision Research Center also aligns with the mission of the UMKC Health Sciences District, a cooperative of 12 neighboring health care institutions on Hospital Hill. Formed in 2017, the partnership supports research, grants, community outreach and shared wellness for employees, faculty, students and surrounding neighborhoods.
According to the Alzheimer’s Association, more than 5-million Americans live with Alzheimer’s disease, which is the sixth leading cause of death in the United States. At UMKC School of Medicine, researcher Peter Koulen, Ph.D., has found an innovative way to diagnose the early stages of the disease – with an eye exam.
The test was developed at the School of Medicine’s Vision Research Center, where Koulen serves as director of basic research. It provides a non-invasive, fast-screening tool for early detection of Alzheimer’s and mild cognitive impairment, a precursor to Alzheimer’s.
Koulen’s work received a patent in January and has been attracting attention since. With support from the university’s Office of Technology Commercialization, it is now drawing interest from local manufacturers and diagnostic companies.
Koulen said the technology has received overtures from local investors interested in forming a startup company to license and further develop it, as well.
“There are business people now on our doorstep,” he said.
The test uses a microperimeter, a machine routinely used in eye exams to evaluate retina function, and typically takes less than half an hour.
And it is a relatively simple test for patients. One looks into the machine and presses a button when they see a flash of light. A computer program progresses through a series of flashing lights in various locations and intensities to measure the person’s retinal function.
“This is a technology that is already widely used by ophthalmologists,” Koulen said. “Over the years, we’ve found some different uses for it, and the Alzheimer’s diagnostics is one example of that. It’s basically a boring video game that you play for a few minutes.”
Because it was developed through clinical studies with patients and subjects, the transition from discovery to use in clinics could be relatively short. Compare that to other research, like creating a cancer drug, which could take decades of development.
“We’ve worked about half a decade on this,” Koulen said.
The technology evolved through researching therapies for glaucoma, macular degeneration and diabetic retinopathy, major eye diseases affecting the retina. These have been the focus of much of Koulen’s work at UMKC since joining the Vision Research Center in 2009.
The retina, a light-sensitive tissue, is part of the body’s central nervous system and is connected to the brain. Koulen and his team spent about seven years developing a still-growing database to define a baseline for healthy retina function. Using microperimetry, they were able to recognize subtle deviations from those baseline figures beyond normal aging. They linked those deviations to what they realized could be indicators of early-stage Alzheimer’s and mild cognitive impairment.
“We were able to pick up that these patients very likely had the neurological disorder before the neurologist was able to diagnose the very earliest forms of the disease,” Koulen said.
There is no single exam for diagnosing Alzheimer’s. The current method is an often cumbersome, time-consuming process of eliminating other potential causes of a neurological disorder. Results can be inconclusive until the disease has progressed to a more-advanced stage. By that point, treatment and patient care has become a primary concern.
A more rapid and conclusive diagnosis is possible with the test Koulen has developed. It can easily be given in a clinic or other settings. That could make the technology enticing for investors.
“The nice thing about conducting the diagnostics in the clinic is that they’re non-invasive,” Koulen said. “You don’t have to draw blood. You don’t need anesthesia. It’s basically a very complicated eye exam, but it’s still an eye exam.”
Researchers at the UMKC School of Medicine Vision Research Center have received nearly $1 million in funding to develop a novel drug that would protect the vision of glaucoma patients.
The five-year, $970,325 project funded by the National Eye Institute at the National Institutes of Health will support efforts led by Peter Koulen, Ph.D., professor and Felix and Carmen Sabates Missouri Endowed Chair at the Vision Research Center. Koulen is also director of basic research at the Vision Research Center.
Glaucoma is the second-leading cause of vision loss in the United States. Once patients are diagnosed with the disease it affects them for the rest of their lives because there is no known cure for the disease. Current therapies used to manage the disease often fail over time, and, therefore, there is a great clinical need for alternative methods that more effectively and safely treat glaucoma and prevent loss of vision.
The new project addresses this urgent clinical need. Focusing on developing a new pharmacological intervention to control the degeneration of nerve cells in the retina caused by glaucoma could help many. More than 3 million Americans suffer from glaucoma. That number is expected to increase to more than 6 million by 2050.
“The resulting medications will potentially be both preventative and therapeutic, while complimenting existing treatments, which lower high pressure in the eye,” Koulen said.
UMKC researchers collaborating on the study are part of a large interdisciplinary consortium of scientists with related expertise in ophthalmology, medicinal chemistry, biopharmaceutics and proteomics.
Preclinical testing of the new therapy, including drug transport and distribution studies, will determine its effectiveness in terminating or possibly preventing glaucoma-associated loss of nerve cells. The goal is to generate data to support the future clinical development and testing of the new drug and move the project to phase 1 or 2 clinical trials.
Determining how and to what extent nerve cells in the retina and visual function are protected including associated biopharmaceutical and pharmacological parameters will indicate the potential of the new drug as an effective glaucoma therapy.
The research is a collaboration with researchers at the University of North Texas Health Science Center under NEI grant #R01EY027005.