Research Program:
The eye presents a unique objective lens through which direct histologic-level observations can be possibly made of neural, glial and vascular tissue in a living human subject. Unfortunately, this special objective lens has a lot of aberrations. Consequently, imaging of retina and optic nerve in the living eye is of surprisingly poor quality. Our research focuses on developing advanced retinal imaging technology that overcomes the defects of the eye to facilitate study of the retinal structure and function in the living mammalian eye at cellular, subcellular and even molecular level, with the promise leading to improved understanding and treatment of human retinal diseases.

The major vehicle taking us to our goal is adaptive optics scanning laser ophthalmoscopy (AOSLO), which is an advanced imaging modality of two-pronged technologies, as indicated by the name, adaptive optics (AO) and confocal scanning laser ophthalmoscope (cSLO). The cSLO is the imaging conductor, which operates with the identical principle of the confocal microscope. AO, was originally designed for compensating the wavefront aberrations caused by the atmospheric turbulence in astronomical imaging, is employed to correct for eye' aberration, allowing in-vivo images of unprecedented resolution and contrast, as shown in the figure. AO is the imaging synergizer.

The left is a single frame taken before AO correction but after the best correction of defocus and astigmatism with trial lenses; the middle is a single frame taken after AO correction, and the right is a image registered from a set of 10 AO-corrected frames. These images were taken from a retinal location about 1° from the fovea center. The field of view is 1.2°, or approximately 360 microns on one side. (Zhang, Y., Poonja, S., Roorda, A., Opt. Lett., 31, 1268-1270, 2006)

AOSLO reveals fine retinal structure characteristics in the diseased human eye such as cone coverage, cone spacing and RPE cells, etc. By control of the intensity of the scanning light beam, the AOSLO can directly project clear visual stimuli with well defined size, structure and intensity onto the retina. Further by tracking the retinal movement, the AOSLO can reliably deliver and keep the stimulus on a single foveal cone transversely in real time. This function significantly facilities microperimetry, functional retinal imaging, psychophysics and high precision electrophysiology studies at single cellular level.

The AOSLO is an excellent platform for incorporating other imaging modalities such as OCT, fluorescence, dark field and high resolution retinal functional imaging to achieve multifunctional and multispectral in-vivo 3-D retinal imaging at the cellular level. With such a system, our basic research targets on small animal imaging for disease models. With the development of the large field of view AOSLO, our patient-oriented research aims at open angle glaucoma (OAG), age-related macular degeneration (ARMD) and other retinal degenerations. We will also study other common medical and neurologic conditions such as hypertension, diabetes, multiple sclerosis (MS), and Alzheimer's disease. Meanwhile, we explore adaptive optics synergized advanced microscopy such as confocal fluorescence imaging, structured illumination and point spread function engineering techniques in histological study of the post mortem retinal tissue, and transfer these methods in imaging of living animal retina and eventually the living human retina.

Our research is funded by the International Retinal Research Foundation and the EyeSight Foundation of Alabama.

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