Structural Comparison of Tree Shrew and Mouse Inner Retina by Visible-Light Optical Coherence Tomography and Confocal Microscopy

Abstract

Purpose : The need for animal models that closely resemble the relevant anatomy and pathologic features of human eye disease is still unmet. Tree shrew eyes share many similar features to human eyes, including a structured lamina cribrosa and fovea-like structure, which allow them to better mimic human pathology than rodent models. In this study, we performed in vivo imaging using visible-light optical coherence tomography (vis-OCT) and ex vivo imaging using confocal microscopy to closely examine the inner retina structural differences in mouse and tree shrew.

Methods : We acquired vis-OCT fibergram images from healthy wild type C57BL/6 mice and tree shrews to visualize the nerve fiber bundles and other inner retinal features. After in vivo imaging, eyes from both animals were sectioned and immunostained with retinal ganglion cell (RGC) axon bundles were labeled with Tuj1, RGC soma were labeled with RBPMS and Brn-3a, and amacrine cells and their processes were labeled by GAD67 and ChAT. Immunostained retinas were then imaged ex vivo with confocal microscopy and compared with resampled vis-OCT images.

Results : RGC axon bundles were more densely packed with elongated and irregular cross sections in tree shrew compared to mice. Resampled circumpapillary vis-OCT B-scans revealed a thicker ganglion cell layer (GCL) in tree shrew compared to mice, which was confirmed by the confocal microscopy images of Brn-3a and RBPMS labeling. In the tree shrew inner plexiform layer (IPL), we identified four sublayers with vis-OCT which correlated with ex vivo confocal images of retinal sections immunostained by GAD67 and ChAT labeling.

Conclusions : Our in vivo and ex vivo imaging revealed major differences between the tree shrew and mouse inner retina anatomy, making tree shrews an ideal model to study eye disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.