Abstract
Purpose: :
To study the progression of retinal degeneration induced by N-methyl-N-nitrosourea (MNU) in a mouse model with high-resolution, spectral domain optical coherence tomography (SD-OCT) and light microscopy.
Methods: :
C57BL/6 mice received a single intraperitoneal injection of MNU at 60 mg/kg. The progression of the retinal degeneration was investigated at 0, 3, 5, 8 and 10 days after MNU treatment by SD-OCT for cross-sectional imaging of retinal structures. Multiple scan averaging was applied to enhance the image of retinal structure. Retinal histology was performed for each time point to correlate the structure findings observed by the SD-OCT images. To identify the apoptotic cells, TUNEL assays were performed on the frozen retinal sections at selected time points (0, 1, 3, 5 days) after the MNU treatment.
Results: :
Following MNU treatment, the retinal thickness progressively decreased with thinning of the outer nuclear layer (ONL) as shown by high quality of SD-OCT images of the mouse retinas. At day 8 after MNU treatment, all the ONL was lost. The sequential decrease in the retinal thickness as observed by the SD-OCT images was confirmed and characterized with the histological data. Moreover, the detachment of the retinal pigment epithelium (RPE) from Bruch’s membrane after the MNU treatment observed in the SD-OCT images was confirmed by the histological analysis. The thinning of the ONL was due to the selective destruction of photoreceptors by the MNU. This result first suggested by the SD-OCT imaging was verified by the observation that TUNEL- positive cells were located at the ONL.
Conclusions: :
The SD-OCT system enabled real-time, non-invasive imaging of the mouse retina. This method allowed in vivo monitoring of the dynamic changes of retinal structures in a mouse model of MNU-induced retinal degeneration. The in-vivo SD-OCT imaging system bridges the gap between research and clinical observations. SD-OCT holds great promise for being an important tool for assessing and monitoring the progression of retinal degeneration and evaluating treatment approaches for retinal trauma and disease.
Keywords: retinal degenerations: cell biology • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • photoreceptors