In vivo retinal imaging in translational regenerative research

Abstract

Regenerative translational studies must include a longitudinal assessment of the changes in retinal structure and function that occur as part of the natural history of the disease and those that result from the studied intervention. Traditionally, retinal structural changes have been evaluated by histological analysis which necessitates sacrificing the animals. In this review, we describe key imaging approaches such as fundus imaging, optical coherence tomography (OCT), OCT-angiography, adaptive optics (AO), and confocal scanning laser ophthalmoscopy (cSLO) that enable noninvasive, non-contact, and fast in vivo imaging of the posterior segment. These imaging technologies substantially reduce the number of animals needed and enable progression analysis and longitudinal follow-up in individual animals for accurate assessment of disease natural history, effects of interventions and acute changes. We also describe the benefits and limitations of each technology, as well as outline possible future directions that can be taken in translational retinal imaging studies.

Keywords: Retinal imaging; adaptive optics (AO); fundus imaging; optical coherence tomography (OCT).

Figure 1

NIR-FAF (A,B,C) and SW-FAF (D,F) imaging of WT, non-dystrophic Long Evens (LE) rats (A,D) and dystrophic RCS rats at age postnatal day [p]28 (B,E) and p84 (C,F). At p28, the SW-FAF signal is weak. At p84, the SW-FAF image of RCS rats is characterized by a strong hyperautofluorescence and the appearance of discrete hypofluorescent lesions surrounded by hyperfluorescent flecks around the optic nerve head. No hypofluorescent lesions are found in LE rats. These hypofluorescent lesions are barely detectable by NIR-FAF (C, red arrow points to a dateable lesion). The figure is modified from our previous publication (55).

Figure 2

Multimodal imaging for longitudinal follow-up of retinal degeneration in RCS rats. SW-FAF imaging (A,D,G) and corresponding SD-OCT scans (B,E,H) of the central retina area in a representative WT, non-dystrophic Long Evans (LE) rat and a single-representative RCS rat at different ages (p28, p84). (C,F,I) A zoomed-in view of the SD-OCT shown in (B,E,H), respectively. The vertical lines in panels (C,F,I) highlight the ONL (red), total retina (yellow) and debris zone [DZ, in blue, panel (F)]. The hypofluorescent lesion detected in the SW-FAF scan [highlighted by red lines, (G)] corresponded to focal loss of the DZ (H,I). The green vertical lines in panels (A,D,G) indicate the position from which the SD-OCT scans on the right were taken.