Researcher Looks at Link between Arthritis and Eye Disease

Holly Rosenzweig, PhD, has developed a novel investigative model that may better inform treatment of patients with ankylosing spondylitis (AS) who also develop uveitis.

Dr. Rosenzweig, who is assistant professor of ophthalmology and joint faculty in the department of molecular microbiology and immunology at Oregon Health & Science University in Portland, worked with a previously established model that used mice immunized with proteoglycan, which causes progressive inflammatory diseases of the joints, as occurs in patients with AS. However, Dr. Rosenzweig was interested in another previously undocumented effect in the models—the development of uveitis.

“We were really excited when we found that the mice tended to develop ocular disease,” she says, “since in many cases, patients with AS develop uveitis. We wanted to study how the eye is susceptible to disease in this context.”

One of the findings of Dr. Rosenzweig’s study was unexpected, and helps illustrate the complex dynamics involved in treating systemic diseases. The study looked at the effect of interferon-gamma on the eye and on joint disease in PG-immunized mice. Interferon has been shown to promote joint inflammation, but the study found it to have the opposite effect on inflammation of the eyes, because it appears to help protect the eyes of mice from contracting uveitis. Mice lacking the gene encoding interferon-gamma were found to develop less severe disease in their peripheral joints and spine. However, somewhat surprisingly, in the same mice lacking interferon-gamma, the uveitis was worse.

“You would think there might be common inflammatory mediators in the eyes, joints, and spine,” Dr. Rosenzweig says. “But in the case of interferon-gamma, they seem to be affected differently.”

As a result, Dr. Rosenzweig’s study may have an impact on the way doctors treat their patients. Ultimately, she wants to find a way to treat both conditions simultaneously. “Ideally, you want to find common mechanisms, because that would be the best therapeutic approach,” she says.

Dr. Rosenzweig has applied for R01 funding from the National Institutes of Health in order to continue her study, but she is quick to point out that she wouldn’t have made it this far without funding from the ACR Research and Education Foundation (REF). She received the ACR REF Health Professional New Investigator Award (now the ACR REF Rheumatology Scientist Development Award), which funded her research from 2009 to 2011.

“It was so important, because I applied without data and with just a novel idea based on preliminary observations,” she says. “It certainly wouldn’t have been suitable for NIH funding at that time. So the REF award was critical for the success of this project and for my independence as a scientist.”