The Influence of NaIO3-Induced Retinal Degeneration on Intra-retinal Layer and the Changes of Expression Profile/Morphology of DA-ACs and mRGCS

Tao, Zui; Dai, Jiaman; He, Jianjun; Li, Chunshi; Li, Yaochen; Yin, Zheng

doi:10.1007/s12035-012-8366-6

Cited by 27 publications

(18 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 Whether or not primary damage occurs in additional retinal structures is still a matter of debate. [14][15][16] However, because it allows controlled onset and progression (for instance, induction in an adult animal), this model may provide benefit for studying novel modalities for treatment of retinal degeneration caused by RPE dysfunction beyond the genetic models that are often used for this purpose.…”

mentioning

confidence: 99%

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

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

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

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…25 Our hypothesis stated that the increased miR-183 cluster in the circulating blood was due to the leakage of RPE and Bruch's membrane by NaIO 3 toxicity. There is a possibility that cells of the neurosensory retina (ganglion cell, amacrine, or horizontal cells) 45 and photoreceptors 46 may also be directly involved in NaIO 3 -mediated toxicity. To date, this is the first report describing the plasma miRNA profile in a nonhuman primate in response to toxic doses of intravenously administered NaIO 3 , therefore the translatability of the nonhuman primate data to the human as well as the neuronal/ neurotrophic factor pathways associated with the neuronal retina injury remains to be explored in future research.…”

Section: Discussionmentioning

confidence: 99%

Ocular safety assessment of sodium iodate in cynomolgus monkeys

Liu

Peng

Yates

et al. 2017

Toxicology Research and Application

View full text Add to dashboard Cite

Although sodium iodate (NaIO 3 )-induced retinal injury model has been widely used in rodents, its application in large animal species has encountered variation in retinal toxicity. NaIO 3 induced retinal degeneration and functional changes in sheep, but not in swine. In monkeys, administration of NaIO 3 via a carotid artery affected only the cell function of ipsilateral retinal pigment epithelium. The aim of the present study was to identify the dosage and route of NaIO 3 administration resulting in morphologic and functional retinal changes in cynomolgus monkeys. Separate groups of animals received NaIO 3 intravenously in three different dosing paradigms. Vehicle control animals received phosphate-buffered saline. At selected time points following dosing, flash electroretinograms (ERGs) were recorded followed by necropsy. The eyes were examined microscopically post-necropsy and the levels of circulating microRNA-183 cluster were evaluated in the blood samples collected on days 1, 4, and 5 postdose. A statistically significant reduction in both scotopic awave and scotopic and photopic b-wave signals (p < 0.05) were observed between the ERG signals acquired from NaIO 3 -treated and vehicle control animals, coupled with time-dependent elevations in plasma miR-183 cluster. Mild to moderate retinal degeneration was observed in the outer layer of the retina, which correlated well with the functional and clinical observations. There were no statistically significant differences in scotopic oscillatory potentials. These findings suggest that intravenous injection of sublethal NaIO 3 markedly damaged the cone and rod photoreceptors both functionally and morphologically, and plasma miR-183 reflected the retinal toxicity in those animals with moderate retinal damage.

show abstract

“…ERG was performed as described previously 61 . Briefly, after 12 hours of adaption to darkness, the animals were prepared for recording under dim red-light (wavelength > 620 nm).…”

Section: Methodsmentioning

confidence: 99%

Improved retinal function in RCS rats after suppressing the over-activation of mGluR5

Dai

Zeng

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine–both inhibitors of glutamine synthetase–subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression. Conversely, activation of mGluR5 by the agonist, (R,S)-2-chloro-5-hydroxyphenylglycine, decreased both the a-wave amplitude and rhodopsin expression, but upregulated expression of Gq alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (Kir) current and decreased the expression of Kir4.1 and aquaporin-4 (AQP4). Further experiments indicated that mGluR5 formed a macromolecular complex with these two membrane channels. Lastly, increased expression of mGluR5 was found in Royal College of Surgeons rats–a model of retinitis pigmentosa (RP). Inhibition of mGluR5 in this model restored the amplitude of ERG features, and reduced the expression of glial fibrillary acidic protein. These results suggest that mGluR5 may be worth considering as a potential therapeutic target in RP.

show abstract

The Influence of NaIO3-Induced Retinal Degeneration on Intra-retinal Layer and the Changes of Expression Profile/Morphology of DA-ACs and mRGCS

Cited by 27 publications

References 42 publications

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

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

Ocular safety assessment of sodium iodate in cynomolgus monkeys

Improved retinal function in RCS rats after suppressing the over-activation of mGluR5

Contact Info

Product

Resources

About