Grant supports research of blood vessels in cancer survivors

Every year, more than 850,000 Americans are diagnosed with some form of cancer, and two-thirds of these patients are treated with radiation therapy. University of Iowa researchers say that while cancer tissue targeting techniques have improved, radiation can still injure healthy tissue surrounding the treatment area.

A team of UI researchers led by Randy Kardon, MD, PhD, professor of ophthalmology and visual sciences, and Isabella Grumbach, MD, PhD, professor of internal medicine – cardiovascular medicine, will study the effects of radiation therapy on small blood vessels, also known as micro vessels, in cancer survivors. The group received a five-year R01 grant for $2.5 million from the National Institutes of Health National Eye Institute.

Many patients after radiation treatment of uveal melanoma experience some degree of vision loss due to the chronic effects of radiation. Using recently developed imaging techniques, researchers will examine radiation injury in the retina’s small blood vessels following treatment of eye melanoma. Laser speckle flowgraphy, a new non-invasive imaging device that measures the dynamics of blood flow in the eye, will be used to identify early changes due to radiation when interventions may prevent vision loss.

“We hypothesize that retinal micro vessel imaging in a living organism is a novel strategy to evaluate normal tissue injury in small blood vessels after radiation treatment for cancer over time and that these imaging techniques can be used as a tool to screen for new drugs that prevent or treat normal tissue injury,” state Grumbach and Kardon.

These new imaging devices allow researchers to measure the blood flow and structure of the small arteries in the eye, which will help identify early signs of blood vessel dysfunction and capillary loss. Investigators will analyze the micro vessels in both patients and mice models with gene alterations.

“We want to find out whether these genes alter the blood flow changes with the big-picture intent to develop new treatments,” shares Grumbach.

To complete their research, Kardon and Grumbach are collaborating with several University of Iowa faculty and departments including H. Culver Boldt, MD, Elaine Binkley, MD (Ophthalmology and Visual Sciences); Mona Garvin, PhD (Biomedical Engineering); Johannes Ledolter (Statistics and Actuarial Science); Timothy Waldron, MS, Michelle Tamplin, MS, Douglas Spitz, PhD, and Bryan Allen, MD, PhD (Radiation Oncology). The grant is a continuum of efforts to build a research area in cardio(vascular) oncology within the Abboud Cardiovascular Research Center at the University of Iowa.

Laser speckle before radiation treatmentLaser speckle post radiation treatment

A color map of blood flow of the retina including the optic nerve before radiation treatment and four months after treatment show a decrease in blood flow (red is high blood flow and blue tones are lower blood flow values).

OCT-A normal capillary density in maculaOCT-A capillary loss in macula from radiation retinopathy

Two optical coherence tomography angiography scans show normal capillary vascular density in the macula of the eye and an example of drop out of capillaries from an eye that occurred slowly over time after radiation treatment of ocular uveal melanoma.

Thursday, June 11, 2020