Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

Abstract

PURPOSE. To characterize the course of sodium iodate (SI)-induced retinal degeneration in young adult albino and pigmented mice. (25, 50, and 100 mg/kg) were performed in 7-to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by optokinetic tracking response, ERG, optical coherence tomography (OCT), and histologic and immunohistochemical techniques. METHODS. Single intraperitoneal (IP) injections of SI RESULTS.The 50 mg/kg SI dosage was selected after dose ranging due to consistent retinal effects and lack of systemic toxicity. Time-dependent deterioration in retinal function and morphology was consistently observed between 1 and 4 weeks in all measured parameters. These include reduction of ERG responses, thinning of retinal layers as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry revealed rapid RPE disorganization with loss of tight junctions and markedly reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone opsins. Earlier time points displayed variable results, including partial recovery of visual acuity at 1 week and supranormal ERG cone responses at 24 hours, suggesting possible limitations of early intervention and assessment in the SI model. CONCLUSIONS.A single IP injection of 50 mg/kg SI leads to severe RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors in both BALB/c and C57Bl/6J mice. This easily induced and reproducible noninherited model may serve as a useful tool for seeking and evaluating novel therapeutic modalities for the treatment of retinal degenerations caused by primary failure of the RPE.Keywords: sodium iodate, RPE toxicity, retinal degeneration, mouse model D iseases such as AMD, Best disease, and subtypes of retinitis pigmentosa RP are major causes of visual disability. 1 In these diseases, primary dysfunction, degeneration, and loss of the RPE ultimately results in secondary death of photoreceptors, leading to visual loss. [2][3][4] Despite certain progress in the treatment of retinal degeneration, it remains an essentially irreversible process in which many patients eventually lose their sight. Animal models provide an invaluable tool for searching and testing of novel therapeutic modalities. Animals carrying natural mutations (usually in one gene) provide well-established models for inherited retinal diseases. 5,6 However, the pathogenesis of multifactorial retinal degenerations such as AMD involves complex genetic and environmental factors, leading to expression of disease at older ages. 7 The majority of geneticallyinherited animal models of ocular disease do not entirely mimic such conditions because of early disease onset and progression. 8 Regardless of etiology, maintaining proper RPE function is a major therapeutic target in these diseases, and currently pharmaceutical, genetic, and cellular approaches are being tested to this end in a variety of in vitro and in vivo models, as well as in clini...

An Acute Injury Model for the Phenotypic Characteristics of Geographic Atrophy

“…The intravenous injection of NaIO 3 creates widespread RPE, photoreceptor, and CC atrophy. 2 – 5 , 17 , 18 This is in sharp contrast to the focal, succinct atrophic areas surrounded by intact, healthy RPE and CC seen in GA. The border region between atrophic and normal tissue is most interesting for studying disease progression of GA, as this is where degeneration is actively occurring.…”

“…For this reason, a well-characterized, cost-effective, and rapid degeneration animal model of GA would be very useful. Sodium iodate (NaIO 3 ) injection has been extensively used as a preclinical model of RPE degeneration and GA. 2 – 5 Different delivery routes and various doses of NaIO 3 have been reported to induce RPE changes in a variety of mammalian species. 2 – 7 NaIO 3 is thought to directly affect the RPE cells with secondary effects on photoreceptors and the CC.…”

“…Sodium iodate (NaIO 3 ) injection has been extensively used as a preclinical model of RPE degeneration and GA. 2 – 5 Different delivery routes and various doses of NaIO 3 have been reported to induce RPE changes in a variety of mammalian species. 2 – 7 NaIO 3 is thought to directly affect the RPE cells with secondary effects on photoreceptors and the CC. It has been shown to induce the production of reactive oxygen species contributing to damage similar to human GA. 8 – 11 The current models using systemic delivery of NaIO 3 , however, result in widespread degeneration.…”

Irreversible Photoreceptors and RPE Cells Damage by Intravenous Sodium Iodate in Mice Is Related to Macrophage Accumulation

“…Many researchers have reported on the time-and dosedependent changes in the NaIO 3 -induced retinal degeneration. 13,19,20 The RPE degeneration induced by NaIO 3 leads to the production of pigment-rich substances, 13,21,22 and both the thickness of the photoreceptor outer and inner segments and the outer nuclear layer are reduced. 13,22 In addition, exposure of the RPE cells to NaIO 3 induces a loss of the integrity of the RPE cells and an enlargement of RPE cells.…”

Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines

“…(2020) 10:3588 | https://doi.org/10.1038/s41598-020-60579-1 www.nature.com/scientificreports www.nature.com/scientificreports/ photoreceptors, SI also provokes choriocapillaris atrophy 27,28 , necrosis of the inner retina 24,29 , and panretinal degeneration 24,30 . It has been reported that various doses and routes of administration of SI cause retinal toxicity in many different experimental animals (e.g., sheep 25 , rabbits 25,31 , rats 30,32 , and mice 23,29,33 ). Most studies have employed relatively high doses of SI (50-100 mg/kg) and have reported rapid RPE damage characterized by the defragmentation and loss of RPE cell nuclei.…”