Retinal degeneration rat model: A study on the structural and functional changes in the retina following injection of sodium iodate

Abstract

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.

Inhibiting microRNA-144 potentiates Nrf2-dependent antioxidant signaling in RPE and protects against oxidative stress-induced outer retinal degeneration

“…Therefore, going forward to in vivo studies, we focused solely on miR-144-3p. We evaluated the impact of miR-144-3p suppression in the sodium iodate mouse model, an established model of pro-oxidant induced outer retinal damage [[28], [29], [30], [31],[46], [47], [48], [49]]. In brief, sodium iodate (50 mg/kg i.p) was used to induce retinal degeneration; anti-miR-144-3p or vehicle (control) was injected sub-retinally on the following day.…”

“…Although, this in vitro study reported a correlation between miR-144 and Nrf2, the specific involvement of 5p or 3p variant and the in vivo effects of miR-144 were not studied. In the present study, we evaluated the relevance of miR-144 to the expression of Nrf2 and downstream Nrf2 target genes in cultured human RPE and, to overall retinal health in the sodium-iodate mouse, a classic rodent model of oxidant-induced retinal degeneration [[29], [30], [31], [32]].…”

Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model

“…Retinal degeneration in post-transplanted (4-day) Sprague-Dawley rats (herein designated as day 0 in the present study) were induced using a systemic administration of sodium iodate (NaIO 3 ) as per our previous study (Koh et al, 2019). The compound was prepared fresh by diluting NaIO 3 (Alfa Aesar, MA, United States) in sterile Hank's balanced salt solution (10% w/v) and stored at RT before administration.…”

“…In this study, we aimed to investigate the therapeutic potential of MSCs EPO in a rat retinal degeneration model that was established using NaIO 3 (Koh et al, 2019). Firstly, MSCs EPO were cultured and expanded until the cells were sufficient enough for intravitreal transplantation into the sodium iodate-induced model.…”

Bilateral retinal toxicity as a result of poisoning with pure iodine

“…It is experimentally capable of forming retinitis pigmentosa or age-related macular degeneration in animals. Also, in these animal studies, sodium iodate at doses of 20 to 80 mg/ kg was used to create retinal toxicity [7]. In an animal study, Moriguchi et al have showed that retinal toxicity, due to sodium iodate, is reversible at low doses and irreversible at high doses [8].…”