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Céline Koster, Anneloor ten Asbroek, Jacoline ten Brink, Reinier O Schlingemann, Jan C van Meurs, Frank D Verbraak, Theo Smit, Camiel Boon, Arthur A Bergen; Sodium iodate-induced retinal degeneration in small animal models for Age-related Macular degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6062. doi: https://doi.org/.
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Age-related macular degeneration (AMD) is a major cause of severe, progressive visual impairment among the elderly. Despite recent great research progress, the detailed pathobiology remains to be elucidated. Research progress is hampered by the lack of suitable in vitro models or animal models which fully represent the AMD phenotype. In this study, we aimed to gain a more precise insight in sodium iodate (NaIO3) induced retinal degeneration in mice and rats as small animal models for AMD.
Animals were anaesthetized using a mixture of Ketamine (10 mg/mL) and Xylazine (1 mg/mL). We performed baseline measurements on four-week-old animals (mice and rats, wildtype and RPE65-/-) using SLO/OCT (Scanning Laser Ophthalmoscopy/Optical Coherence Tomography; Heidelberg) and ERG (Electroretinography; DORC) to check overall morphology, detailed structure and function of the retina. NaIO3 was injected intravenously in a concentration range of 0-100 mg/kg (n=4 per group). The animals were followed using SLO/OCT and ERG. ERG responses were analyzed using the amplitudes of a- and b-waves as well as latency times. At various time points, animals were sacrificed and their eyes harvested for immunohistochemistry analyses. We compared the ex vivo and in vivo data per animal(group).
Following NaIO3 injection, the photopic and scotopic ERG amplitudes of a- and b-waves were (strongly) decreased after one week, due to deterioration of the RPE and photoreceptors with little variability within groups. The control groups (0 mg/kg) in both RPE65-/- and wildtype animals did not show any retinal degeneration as seen by OCT, while the experimental groups did.Structural retinal degeneration, both in RPE65-/- mice and in wildtype controls, was only seen after injecting more than 10 mg/kg of NaIO3. Rapid degeneration of the retina was observed in groups receiving more than 50 mg/kg. The OCT data were confirmed by immunohistochemistry analyses. We also compared the effects of NaIO3 in RPE65 knock-out animals and wild-type controls.
We gained more insight on the NaIO3-induced retinal degeneration in animal models for AMD (mice and rats). We were able to evaluate the functional and structural changes of the (degeneration of the) retina in these animals over time, non-invasively. No difference could be observed between RPE65 knockout and wildtype animals based on the morphology of their retina’s.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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