| dc.description.abstract | BIOMEDICAL ENGINEERING
QUANTUM DOT-BASED IN VIVO IMAGING OF INFLAMMATION
ASHWATH JAYAGOPAL
Thesis under the direction of Professor Frederick R. Haselton
The recruitment of leukocytes to tissue and their specific interactions with adhesion molecules are essential processes which provide for a natural mechanism of localizing immune defense. However, inappropriate immune responses can manifest as harmful inflammation in a variety of diseases. Much information has been derived from immunohistochemistry and in vitro cell culture studies, which have identified various inflammatory mechanisms and mediators. A key challenge has been the in vivo investigation of detailed cellular and molecular events in real-time, such as leukocyte extravasation. A variety of cell adhesion molecules and cell types facilitate these activities, and the ability to monitor their recruitment and proliferation would likely have an impact on the development of diagnostic and therapeutic avenues. Current imaging techniques to characterize these events are limited by low signal to background ratios, invasiveness, and fading. In this study, we use fluorescence microscopy and quantum dot-antibody conjugates to specifically investigate the expression of the cell adhesion molecule VCAM-1 in diabetic rats. The retina was used to non-invasively probe inflammatory activity in the circulation, and to investigate the impact of diabetes-induced inflammation on ocular complications. We report elevated VCAM-1 levels in diabetic rats relative to untreated controls. In addition, we observed ex vivo and in vivo quantum dot-labeled leukocytes in the healthy and diseased retinal circulation. Features of this technique include stable, high intensity of labeled species and a narrow, size-tunable emission spectra. These studies demonstrate the promise of quantum dots in the in vivo visualization of molecular and cellular inflammatory mediators.
Approved: Date:
Frederick R. Haselton 7/29/05 | |
