Abstract
Purpose::
To investigate alterations of morphology and function in Nrl deficient mice (Nrl-/-) over a period of one year.
Methods::
Nrl-/- mice were studied in vivo at the age of 1, 2, 5, 7, and 12 months and results were compared to histological findings. Retinal function was evaluated with Ganzfeld electroretinograms (ERGs; Multiliner Vision, VIASIS, Germany) recorded under dark- and light-adapted conditions. A HRA I scanning-laser ophthalmoscope (SLO; Heidelberg Engineering, Germany) was used for in vivo imaging. The study was performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Visual Research.
Results::
In Nrl-/- mice, the scotopic and photopic ERG waveform shapes were very similar due to the complete absence of rod-mediated responses. However, Nrl-/- mice were also about 10-fold less sensitive to light than mice deficient in rhodopsin (Rho-/-), which also lack rod signals. In contrast, the b-wave amplitude maximum of Nrl-/- mice at age of one month was 2-3 times larger than that in Rho-/- mice at the same age. These supernormal cone responses declined slowly with age; at 12 months only about 1/3 of the initial b-wave amplitude remained. In parallel, multiple depigmented lesions of the RPE were apparent in SLO imaging, presumably resembling the sites of rosette formation. These lesions often showed fluorescein leakage taken up by retinal veins, indicating the passage of choroidal fluid into the retina. These findings correlated well with the histological results: distinct layers of retina were heavily disorganized and disrupted by rosette-like, dysmorphic structures surrounded by cones. From about 3-5 months on, more contiguous areas of damage developed at the expense of single lesions.
Conclusions::
A severe, progressive degeneration of retinal morphology and function was found in Nrl deficient mice over a period of one year.
Keywords: electroretinography: non-clinical • photoreceptors • retina