In vivo imaging of the mouse model of X-linked juvenile retinoschisis with fourier domain optical coherence tomography

Abstract

Purpose: The purpose of this study was to investigate Fourier domain optical coherence tomography (FD OCT) as a noninvasive tool for retinal imaging in the Rs1h-knockout mouse (model for X-linked juvenile retinoschisis).

Methods: A prototype spectrometer-based FD OCT system was used in combination with a custom optical beam-scanning platform. Images of the retinas from wild-type and Rs1h-knockout mice were acquired noninvasively with FD OCT with the specimen anesthetized. At the completion of the noninvasive FD OCT imaging, invasive retinal cross-sectional images (histology) were acquired from a nearby region for comparison to the FD OCT images.

Results: The retinal layers were identifiable in the FD OCT images, permitting delineation and thickness measurement of the outer nuclear layer (ONL). During FD OCT in vivo imaging of the Rs1h-knockout mouse, holes were observed in the inner nuclear layer (INL), and retinal cell disorganization was observed as a change in the backscattering intensity profile. Comparison of the ONL measurements acquired noninvasively with FD OCT to measurements taken using histology at nearby locations showed a degeneration of roughly 30% of the ONL by the age of 2 months in Rs1h-knockout mice relative to wild-type.

Conclusions: FD OCT was demonstrated to be effective for noninvasive imaging of retinal degeneration and observation of retinal holes in Rs1h-knockout mice.

Figure 1

Schematic diagram of the FD OCT interferometric setup used to image the mouse retina.

Figure 2

Comparison of the wild type mouse retinal layers observed in (a) DAPI stained histological section merged with DIC to (b) non-invasive FD OCT. The retinal layers were segmented manually and a fit to a fourth order polynomial which was subsequently used for the thickness measurement. Arrows point to holes observed in the inner nuclear layer (INL) of (c) DAPI stained histology and (d) FD OCT image of the retina of a two month old Rs1h knockout mouse. GCL, ganglion cell layer; IPL, inner plexiform layer; OPL, outer plexiform layer, ONL, outer nuclear layer; IS, inner segment; OS, outer segment.

Figure 3

Fundus-type images reconstructed from FD OCT data acquired from (a) WT and (b) Rs1h KO mice. DAPI stained histology and FD-OCT images from the same mice are shown for (c, d) 2 month old WT, (e, f) 2 month old Rs1h KO, (g, h) 15 month old Rs1h KO.

Figure 4

(a) ONL thickness of wild type and Rs1h KO mice measured with FD OCT for different age groups. Two dimensional map of the ONL thickness for (b) wild type and (c) Rs1h knockout mouse at two months of age.