Uveitis/Inflammatory Disease Research;
Inflammatory diseases of the eye range from the annoying allergic conjunctivitis of hay fever to potentially blinding uveitis. Researchers at the Casey Eye Institute are working to improve the efficacy and safety of treatment for these diseases.
These studies involve:
- clinical trials to compare determine the effectiveness of newer and more established various medications in patients with uveitis andor other ocular inflammatory disease
- a search for genes that make some people more likely to get uveitis, and
- experiments to help us understand how the diseases develop.
The Casey Eye Institute is one of the world's leading uveitis research centers, with encompassing research in basic science and clinical trials and, translating “bench” research discoveries to the bedside to benefit our patients.
What are inflammation and uveitis?
Uveitis and other forms of inflammation are a result of our immune system trying to protect us from infection.
Uveitis is a descriptive term that includes a group of diseases with inflammation inside the eye.
Common to all inflammatory diseases is the migration of specific types of white blood cells and some plasma proteins out of the blood stream into surrounding tissues. These cells release agents to boost immune responses and kill invading bacteria, viruses, and parasites. Unfortunately, normal healthy tissue can also be injured by inflammation, and the affected region may become red, sore, and swollen. Too much inflammation inside an eye can cause loss of vision.
Inflammation is a complex process involving many different kinds of cells. Endothelial cells line the blood vessels and serve as the gatekeepers that control the emigration of white blood cells and plasma proteins from the blood stream. During inflammation, endothelial cells in small blood vessels called venules will snare passing cells, making them roll and eventually stick to the inside of the venule. If the trapped cell is the kind being sought by the endothelial cells, its molecular motors will be turned on. It will squeeze between the endothelial cells to get out of the blood. Then it will move through the tissue and the ocular fluids looking for bacteria, viruses, or foreign substances.
How do the endothelial cells know when to catch a particular kind of white blood cell? Many kinds of cells when injured will send signals to the endothelial cells. Sentinel cells known as dendritic cells and macrophages can detect invading bacteria. Dendritic cells are particularly adept at getting the kind of white blood cells known as lymphocytes to recognize and generate immune responses to foreign substances. Mast cells can be turned on by allergens, such as ragweed pollen or cat dander, to trigger endothelial cells in allergic conjunctivitis.
Before the U.S. FDA (Food and Drug Administration) approves a new medication or a new use of an existing medication, its effectiveness and safety need to be evaluated in carefully designed clinical trials. With one of the largest Uveitis Clinics in the country, the Casey Eye Institute is an important part of multicenter studies of new therapies for uveitis, as well as a site where innovative therapies are trialedtested in smaller, single-center clinical trials. Patients come from all over the Pacific Northwest for specialized care that might include experimental drugs. For a complete list of active clinical trials underway at the Casey Eye Institute, search www.clinicaltrials.gov or contact our Clinical Trials Manager at 503-494-0482.
For some types of uveitis, if one member of a family is affected, then other members of the family are more likely to have uveitis too. There is no evidence to suggest that bad genes cause uveitis, but rather that some genes increase the chances that a person will develop uveitis. One gene, called HLA-B27, is known to increase a person's risk of getting uveitis as well as some forms of arthritis and spondylitis. Preliminary studies indicate that there are other genes that also increase a person's chances of getting uveitis.While the genetic risk for disease associated with HLA-B27 is high, we know that several other genes also contribute to a predisposition to uveitis.
Researchers at the Casey Eye Institute have embarked on a projects to identify the other genes that increase the risk of getting uveitis. Family histories and blood for DNA analysis are being collected from uveitis patients throughout the United States, Canada, and Europe.
If your family has two or more individuals who you suffer from uveitis or iritis, then we invite you to participate in this study. Family histories, medical records and blood for DNA analysis are being collected from uveitis patients throughout the United States, Canada, and Europe. We especially need families with siblings (i.e., brothers and sisters) who have this disease. You will not personally benefit from participating in this study. However, by participating as a subject, you may contribute new information that we believe will benefit patients in the future. If you wish to participate or have questions about the study, please contact the study coordinator (503-494-3689 or toll-free in the U.S. at 866-338-6789) or send e-mail to firstname.lastname@example.org.
The Casey Eye Institute is a leader in genetic research on eye diseases that include age-related macular degeneration and glaucoma in addition to uveitis.
Ocular Immunology Laboratory
The Ocular Immunology Laboratory at Casey Eye Institute offers retinal autoantibody tests for cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), autoimmune retinopathy and optic neuropathy. Find more information on these conditions or learn how to send a sample to our lab for testing.
Current therapies for uveitis and other diseases of ocular inflammation can have unwanted side effects or adverse reactions. Many of the medications used today will reduce the patient's symptoms but not cure the disease. To look for new medications with fewer side effects or increased effectiveness, we need to learn the basic mechanisms in each step of the disease process.
Inflammation and immunology research at the Casey Eye Institute is multifaceted. Different forms of uveitis, and allergic conjunctivitis, corneal inflammation, and the interrelationship between corneal inflammation and tear production are all under study. Because uveitis is sometimes associated with inflammation elsewhere in the body, we also study inflammatory arthritis. The primary focusfocal points for each of these projects areis to determine the type and exact location of the cells actively involved at each stage of disease, and how these cells communicate or interact with each other, and how signaling networks inside the cells respond to different pathogen sensors. Cell-to-cell communication signals are often effective targets for medications to alter the course of a disease. Intracellular signaling molecules may also prove to be useful therapeutic targets. Comparing the inflammatory processes in eyes and joints allows us to distinguish those processes that are general in nature and those that are tissue-specific. This information should allow fine tuning of therapies to minimize side-effects.
These projects use modern techniques in cell and tissue culture, molecular genetics, genetically altered rodents, and microscopy. For example, researchers at the Casey Eye Institute were the first in the world to prepare pure cultures of endothelial cells from human iris. These cells, as described above, are important gatekeepers in uveitis in the front of the eye (iritis). Subtle differences between these iris endothelial cells and those from other parts of the eye and body might account for the tissue-specificity of some diseases. The powerful techniques of gene cDNA gene expression microarray and proteomic analyseis have beenis being used to screen hundreds to thousands of endothelial cell genes for tissue-specific differences. Blood from patients and control subjects is being screened to determine if different diseases can be associated with unique patterns of gene activity.
A gene of particular interest to us is called NOD2. Individuals with mutations in some parts of the gene get a disease called Blau Syndrome that results in inflammation of eyes, joints, and skin. Mutations in other parts of the gene increase a person’s risk of getting Crohn’s Disease that affects the gut. The NOD2 protein is part of a signaling system involved in a cell’s response to bacteria. Learning how NOD2 is supposed to work and what goes wrong with the mutated protein should not only help devise effective therapies for patients with Blau Syndrome or Crohn’s disease, it will also help our basic understanding of an intricate intracellular signaling network.
The Casey Eye Institute is also a world pioneer in applying the technique of intravital microscopy to watch cells at work in the eyes of living rodents and people. This is a non-surgical procedure that can be safely used to monitor the activity of the immune system in and around individual blood vessels or individual cells as a disease progresses. Both real-time and time-lapse movies can be recorded for detailed analysis
Uveitis Fellowship Program
We offer a one-year fellowship marrying an intensive experience in clinical uveitis with exposure to our basic science programs, with independent or mentored research projects strongly recommended. Graduates of our fellowship program have gone on to fill faculty positions at academic institutions in the United States and internationally.If you are interested in applying for our fellowship please find the application requirements at www.sfmatch.org. Further questions may be directed to our office.
The ocular inflammation and immunology research group is funded by grants from the National Eye Institute branch of the National Institutes of Health, from nonprofit organizations, for example Research to Prevent Blindness and Fight for Sight the Fight for Sight research division of Prevent Blindness America. Some clinical trials are done under contract with a pharmaceutical company.
Contributions from private individuals are important also. The tax deductible contributions are used directly for projects such as those described above. They also enable medical students, college students, and high school students an opportunity to work in the laboratory and experience the challenges of biomedical research. Donations to the Oregon Health Sciences Foundation should be mailed to:Uveitis Research
Attn: Dr. James Rosenbaum
Casey Eye Institute
3375 SW Terwilliger Blvd
Portland, OR 97239