Russ Van Gelder, MD, PhD
Boyd K. Bucey Professor and Chair
Tami Lamprecht, MS, Research Scientist
Lakshmi Akileswaran, PhD, Research Scientist
Angela Sandt, Lab Technician
Tim , Doctoral Student
I. We are developing a novel DNA-based method for discovering pathogens in idiopathic ocular inflammation. Using a special class of restriction enzymes, a library of short nucleic acids fragments (“tags”) that represents all DNA in a tissue sample is created. Hundreds of thousands of tags are retrieved from each sample and sequenced using high-throughput sequencing technology. Non-human sequences are identified from this “digital karyotype,” and matched to the organism from which they originate. Using this technique, we can uncover infectious etiologies of poorly understood eye diseases, allowing for targeted therapy. As sequencing technology improves, this method will be used clinically to diagnose infection, much like ordering blood cultures.
II. Most blindness in the US is due to degeneration of photoreceptors, including hereditary and age-related retinal degeneration. Strategies for treating these diseases include slowing photoreceptor degeneration, electrically stimulating healthy retinal ganglion cells and employing stem cell-based technology to replace lost cells. These approaches are still in early development, and face formidable technical challenges. Azobenzene compounds are phot-isomerizable molecules that can be employed as nano-switches. When coupled to pharmacologic agents, these molecules can be employed as photo-activatable ligants. Azobenzene depolarization of neurons expressing a broad range of potassium channels, effectively converting neurons into photoreceptors.
Chronic ocular inflammation or uveitis is a sight-threatening and potentially blinding disease. Uveitis can often be classified into two categories, granulomatous and nongranulomatous on the basis of appearance of white blood cells in the eye. This categorization can be determined by the eye examination without any specifments being removed for pathology analysis. Unfortunately, other than a few infectious causes of uveitis, the underlying cause of many cases of granulomatous uveitis is unknown.
Some cases of granulomatous uveitis can be attributed to the disease sarcoidosis. This is a multi-system disease in which small nests of white blood cells (granulomas) form in multiple tissues in the body (most commonly in the lung and the eye). Until recently, the only way to diagnose sarcoidosis was to obtain a tissue biopsy (usually from the lung) and look for the characteristic appearance of the white blood cells in the tissue.
Recent studies have shown that certain bacterial proteins may be associated with systemic sarcoidosis. The white blood cells of patients with sarcoidosis are much more likely to react to one particular bacterial protein (mycobacterial catalase) than the blood of patients who do not have this disease.
Our study is designed to determine what fraction of patients with granulomatous uveitis vs. non-granulomatous uveitis have reactivity to mycobacterial catalase. The goal is to generate a blood test for ocular sarcoidosis to replace the need for biopsy to make this diagnosis.