Sodium iodate-induced retina degeneration observed in non-separate sclerochoroid/retina pigment epithelium/retina whole mounts

Abstract

Background: Sodium iodate (SI) is a chemical widely applied to induce retina degeneration in animal models. SI treatment caused formation of rosettes/folds in the outer nuclear layer (ONL) of the rat retina, but it was previously unclear whether SI also forms rosettes in mice. In addition, SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount. Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts. Methods: SI was intraperitoneally injected in Sprague-Dawley (SD) rats and C57BL/6J mice using a single dose (50 mg/kg) or with a dose range (10 to 50 mg/kg) in BALB/C mice. Rat retinas were investigated up to 2-week post-injection by histology and whole mounts, and mouse retinas were investigated up to 3-week post-injection by histology, fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage. Results: SI-induced retina damage caused photoreceptor (PR) degeneration and rosettes/folds formation, as well as retina pigment epithelium degeneration and inward migration. It displayed mixed nuclei from choroid to PRs, due to layer disorganization, as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts. Measurement of the PR rosette area induced by SI provided a quantitative, morphological evaluation of retina degeneration. Conclusions: The method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers, which cannot be addressed by using sectioned and separate whole mount methods. This method is applicable for morphological evaluation of retina damage, especially in the subretinal layer.

Combination of Lactobacillus fermentum NS9 and aronia anthocyanidin extract alleviates sodium iodate-induced retina degeneration

“…In the Control and Model groups, rats were orally administrated with distilled water. The murine NaIO 3 injection model is a widely used AMD model 16 – 18 and we had confirmed 30 mg/kg body weight as an appropriate dose in our preliminary experiment. A single treatment of NaIO 3 at 30 mg/kg body weight was intravenous injected in the Model, AAE and AAE + LF groups on the 8th day.…”

“…Sodium iodate (NaIO 3 ) is an oxidative agent, and it can induce selective RPE damage. The murine NaIO 3 model has been widely used to study dry AMD since it results in reproducible, patchy retinal degeneration 16 – 18 .In this study, we investigated the effects and possible mechanisms of aronia anthocyanidin extract (AAE) together with L. fermentum NS9 (LF) on rat retina in the NaIO 3 induced dry AMD model, in comparison with AAE treatment alone.…”

Comparison between sodium iodate and lipid peroxide murine models of age-related macular degeneration for drug evaluation—a narrative review

“…The fluorescent intensity of opsin expressions – Rho, S-opsin, M-opsin - is further observed and measurable by immunofluorescence staining in sectioned and whole mount retinas ( 28 , 34 , 63 ). In sodium iodate model of retina degeneration, number and area of photoreceptor folds/rosettes are measurable in retinal sections ( 48 ) and sclerochoroid/RPE/retina whole mounts, and the representative images of the rosettes induced by sodium iodate in sclerochoroid/RPE/retina whole mounts can be seen in a paper published in this journal ( 49 ) ( Figure 3C ).…”

“…Sodium iodate-induced retina degeneration has been widely applied to different animal species, including rabbit, sheep, dog ( 47 ) and mouse via the administration routes of tail ( 26 ) or femoral vein ( 48 ), retro-orbital venous sinus ( 30 ), intraperitoneal ( 34 ), subretinal ( 29 ) and/or intravitreal ( 28 ) injections ( Figure 1 ). Systemic injection of sodium iodate induces acutely RPE degeneration within a day, and increasing photoreceptor degeneration, followed by outer nuclear layer rosettes formation, but no significant damage in other retinal layers ( 49 ) ( Figure 2 ). On the other hand, lipid peroxides were applied to New Zealand rabbits ( 38 ) and Sprague-Dawley (SD) rats via the administration routes of intravitreal and subretinal injections ( 2 , 37 ).…”

“…In this section, ERG as a non-invasive measurement is described, and the invasive assessment of retinal thickness, photoreceptor loss, outer nuclear layer folds, RPE loss, subretinal microglia infiltration, and expression of inflammatory, oxidative and cell death genes are discussed. Moreover, the benefits of the sclerochoroid/RPE/retina whole mount application to observe the flat view of the disorganized subretinal and outer nuclear layers ( 49 ), and the infiltrated subretinal microglia ( 54 , 55 ) are discussed.…”