Functional Optical Coherence Tomography of Stimulus-Evoked Intrinsic Optical Signals in the Retina

2018-02-08T00:00:00Z (GMT) by Benquan Wang
Retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), etc., can produce photoreceptor and/or inner neural dysfunctions that lead to severe vision loss or even legal blindness if not diagnosed and treated promptly. It is known that different retinal diseases target different retinal cell types. Therefore, high-resolution assessment of retinal neural function is desirable for early detection of retinal diseases. Stimulus-evoked intrinsic optical signal (IOS) changes, which show tight correlation with retinal physiological dynamics, have been observed in animal and human retinas, promising a high-resolution method for functional imaging of retinal neural function. For testing clinical potential of functional IOS imaging, this dissertation was designed to achieve in-depth understanding of IOS sources and mechanisms, and to demonstrate in vivo IOS mapping of retinal neural dysfunctions in animal models. Three custom-built imaging systems, line-scan time domain optical coherence tomography (TD-OCT), hybrid line-scan confocal microscope and spectral domain OCT (SD-OCT), and in vivo SD-OCT, were employed for both in vitro and in vivo investigation of amphibian (frog) and mammal (mouse) retinas. In vitro OCT of frog retinas revealed rapid IOS response, almost immediately (<3 ms) after the onset of visible light flashes, at photoreceptor outer segment (OS). Quantitative analysis indicated that the fast IOS may originate from G-protein binding and releasing in early phases of phototransduction. In vivo OCT imaging of mouse retinas confirmed fast IOS in photoreceptor OS and slow IOS in inner retinal layers. Comparative IOS and ERG study indicated that the fast IOS in photoreceptor OS may be attributed to the early stage of phototransduction before the hyperpolarization of retinal photoreceptor. Using the hybrid confocal-OCT imaging system, transient OS change was identified as a major contributor to the fast IOS observed in retinal photoreceptors, predominantly in rods. In vivo OCT imaging of retinal degeneration 10 (rd10) mice revealed localized IOS distortions and morphological abnormalities. Comparative ERG recording disclosed consistent abnormalities in the ERG a-wave. The potential for using functional IOS imaging for early detection and progression monitoring of retinal photoreceptor degeneration was demonstrated with the mutant rd10 mouse model.