Optical Coherence Tomography in Mouse Models of Retinal Degeneration

Abstract

Purpose: : Recent technical advances in optical coherence tomography (OCT) make the examination of very small eyes like those of mice a worthwhile endeavour. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration in vivo.

Methods: : Wild-type animals and several lines of mice with known alterations of retinal morphology were subjected to spectral domain OCT (SD-OCT) using commercial equipment (Heidelberg Engineering Spectralis^TM). Results were compared to standard histology.

Results: : We found that in wild type mice, the laminar architecture and retinal thickness correlated well with the histological pattern ex vivo. Alterations were studied in models where with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb (Chen et al. 2006), the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In NRL knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like inflammatory edema. In Crb1 knockout mice (a model for Leber’s congenital amaurosis), retinal vessels slipping through the outer nuclear layer down to the RPE due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identifed.

Conclusions: : We found that the resolution in 3^rd generation OCT systems is sufficient to obtain almost histology-analogue sections of the retina even in rodent eyes. In addition, it may also provide information not available ex vivo (like sites of edema). These results indicate that OCT clearly has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical assessment of therapeutic strategies. In this context, OCT certainly will also help to reduce the numbers of study animals needed.

Keywords: retinal degenerations: cell biology • retinal degenerations: hereditary • imaging/image analysis: non-clinical