Noninvasive, In Vivo Assessment of Mouse Retinal Structure Using Optical Coherence Tomography

Abstract

BackgroundOptical coherence tomography (OCT) is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration.Methodology/Principal FindingsWe achieved to adapt a commercial 3rd generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, 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 edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis), retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE) due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified.Conclusions/SignificanceWe found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical assessment of therapeutic strategies.

Tomographic fundus features in pseudoxanthoma elasticum: comparison with neovascular age-related macular degeneration in Japanese patients

“…[24][25][26][27] In the retina of Nrl knockout mice, Fischer et al 24 show that the histology of rosette structures corresponds with the round or ovoid features with highly reflective annular lines observed in speckle noise-reduced SD-OCT. Although it remains unclear whether the rosettes in animal models are same as the ORT in human patients, 26 this correspondence suggests that the ORT is comprised of rearranged neuronal cells.…”

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“…Eyes were treated with 1% atropine to ensure pupil dilation. Images were taken as described previously (53). The parameters evaluated were number of main blood vessels (fundus), retinal thickness, and morphology of retinal layers.…”

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