All ETDs from UAB

Advisory Committee Chair

Xincheng Yao

Advisory Committee Members

Franklin R Amthor

Christine A Curcio

Lei Liu

Steven J Pittler

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

The objective of my PhD dissertation research is to explore high resolution imaging of retinal function using transient intrinsic optical signals (IOSs) correlated with retinal physiological activation. The retina is responsible for capturing photons and preliminary visual information processing. Functional examination of retinal neural cells is important for eye disease detection and treatment evaluation. It is known that different diseases can target different retinal cell types, and thus high resolution imaging of retinal function is desirable. Fast IOSs with time courses comparable to retinal electroretinogram (ERG) kinetics can act as a unique biomarker to map physiological distortions correlated with eye diseases. In vitro IOS imaging of wild-type and mutant mouse retinas has revealed IOS distortions correlated with retinal diseases. In order to achieve in vivo IOS imaging, a rapid line-scan confocal ophthalmoscope was constructed. Confocal IOS imaging of laser-injured frog eyes unambiguously detected localized (30 &mum) functional lesions in the retina before morphological abnormality is detectable. Comparative IOS and ERG measurement revealed a close correlation between the observed optical response and retinal electrophysiological dynamics, particularly the ERG a-wave, which has been widely used to evaluate photoreceptor function. To further uncover the anatomic source of fast IOSs in retinal photoreceptors, a functional spectral domain optical coherence tomography (SD-OCT) system was constructed to provide depth-resolved IOS mapping at subcellular resolution. High spatiotemporal resolution OCT disclosed that fast IOSs was predominantly confined to the outer retina, particularly in the photoreceptor outer segment. Comparative study of dark- and light-adapted retinas demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, with great potential for early disease detection and improved treatment evaluation of age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage. In addition to functional retinal imaging, we also applied the SD-OCT system for in vivo dynamic observation of light-driven melanosome translocation in RPE. Comparative OCT examination of dark- and light- adapted frog eyes verified that RPE melanosomes are the primary source of reflectivity in the RPE band. To the best of our knowledge, this is the first time demonstration of the feasibility of dynamic OCT monitoring of sub-cellular RPE translocation. Thus, SD-OCT is a versatile tool to assess posterior segment dynamics that may have relevance in the clinical setting.

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