Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography.

Abstract

BACKGROUND:

Optical 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 FINDINGS:

We achieved to adapt a commercial 3(rd) 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/SIGNIFICANCE:

We 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.

• Authors: M Dominik Fischer, Gesine Huber, Susanne C Beck, Naoyuki Tanimoto, Regine Muehlfriedel, Edda Fahl, Christian Grimm, Andreas Wenzel, Charlotte E Remé, Serge A van de Pavert, Jan Wijnholds, Marek Pacal, Rod Bremner, Mathias W Seeliger
• Journal: PloS one (PLoS One) Vol. 4 Issue 10 Pg. e7507 (Oct 19 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19838301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic-Leucine Zipper Transcription Factors
• Crb1 protein, mouse
• Eye Proteins
• Nerve Tissue Proteins
• Nrl protein, mouse
• Retinoblastoma Protein

Topics

• Animals
• Basic-Leucine Zipper Transcription Factors (genetics)
• Eye Proteins (genetics)
• Female
• Lasers
• Light
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nerve Tissue Proteins (genetics)
• Ophthalmoscopy (methods)
• Retina (metabolism)
• Retinal Degeneration (metabolism)
• Retinoblastoma Protein (genetics)
• Tomography, Optical Coherence (methods)