Sodium-Iodate Injection Can Replicate Retinal Degenerative Disease Stages in Pigmented Mice and Rats: Non-Invasive Follow-Up Using OCT and ERG

Abstract

Purpose: The lack of suitable animal models for (dry) age-related macular degeneration (AMD) has hampered therapeutic research into the disease, so far. In this study, pigmented rats and mice were systematically injected with various doses of sodium iodate (SI). After injection, the retinal structure and visual function were non-invasively characterized over time to obtain in-depth data on the suitability of these models for studying experimental therapies for retinal degenerative diseases, such as dry AMD. Methods: SI was injected into the tail vein (i.v.) using a series of doses (0–70 mg/kg) in adolescent C57BL/6J mice and Brown Norway rats. The retinal structure and function were assessed non-invasively at baseline (day 1) and at several time points (1–3, 5, and 10-weeks) post-injection by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and electroretinography (ERG). Results: After the SI injection, retinal degeneration in mice and rats yielded similar results. The lowest dose (10 mg/kg) resulted in non-detectable structural or functional effects. An injection with 20 mg/kg SI did not result in an evident retinal degeneration as judged from the OCT data. In contrast, the ERG responses were temporarily decreased but returned to baseline within two-weeks. Higher doses (30, 40, 50, and 70 mg/kg) resulted in moderate to severe structural RPE and retinal injury and decreased the ERG amplitudes, indicating visual impairment in both mice and rat strains. Conclusions: After the SI injections, we observed dose-dependent structural and functional pathological effects on the retinal pigment epithelium (RPE) and retina in the pigmented mouse and rat strains that were used in this study. Similar effects were observed in both species. In particular, a dose of 30 mg/kg seems to be suitable for future studies on developing experimental therapies. These relatively easily induced non-inherited models may serve as useful tools for evaluating novel therapies for RPE-related retinal degenerations, such as AMD.

Sub-Retinal Injection of Human Lipofuscin in the Mouse - A Model of “Dry” Age-Related Macular Degeneration?

“…Another model to mimic pathological changes of AMD in small rodents was to inject sodium iodate (NaIO 3 ), subretinally [29] or into the systemic circulation [30]. After subretinal injection, NaIO3 causes a strong oxidative stress, and a quick degeneration of the RPE, adjacent photoreceptors and underlying choriocapillaris was observed [29].…”

“…After subretinal injection, NaIO3 causes a strong oxidative stress, and a quick degeneration of the RPE, adjacent photoreceptors and underlying choriocapillaris was observed [29]. After systemic application, deleterious effects on retinal structure and function became visible after a longer time, detected by OCT imaging and ERG measurements, depending on the applied dose of NaIO 3 [30].…”

“…As subretinally injected LF distributed only over a small part of the back of the eye, it may not be surprising that we did not see bigger differences to PBS injection in the ERG measurements and the qPCR analysis. In further studies, possible changes in ERG parameters should be monitored of a longer duration, such as it was done by Koster et al [30].…”

Modeling aging and retinal degeneration with mitochondrial DNA mutation burden

“…Additionally, since there was a distinct preferential loss of complex proteins, mtDNA sequencing analysis of this tissue could provide more evidence for ETC dysfunction and how it is correlated to specific mtDNA point mutations in different regions of the mitochondrial genome. Finally, this model should be combined with other developed retinal degeneration models to identify its susceptibility to oxidative or light-induced damage (Koster et al, 2022; Wang et al, 2023). Overall, this study identifies the importance of the preservation of mtDNA in the aging mouse retina and the vulnerabilities that dysfunction of this system presents to retinal health.…”

Multi-Wavelength Photobiomodulation Ameliorates Sodium Iodate-Induced Age-Related Macular Degeneration in Rats

“…But in this aged control animal, an age-related change in the macular could exist even without any pharmacologic agents. As such, many studies, along with our own, used young age rats to induce AMD in animal models [38,39]. The experimental design of 7 days also requires additional discussion.…”