Fundus autofluorescence (FAF) non-invasively identifies chorioretinal toxicity in a rat model of retinal pigment epithelium (RPE) damage

Baek, David Sung Hyeon; Liang, Hao; Zhao, Xu; Pankova, Natalie; Wang, Hai; Boyd, Shelley

doi:10.1016/j.vascn.2014.09.002

Cited by 12 publications

(7 citation statements)

References 27 publications

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“…Recently, the cumulative size of abnormal retinal FAF in SI-exposed albino rats was shown to correlate with the SI dose, and inversely correlate with ERG b-wave amplitudes. 35 In BALB/c mice, a few hyperfluorescent spots were already apparent at baseline (Fig. H1).…”

Section: Course Of Sodiummentioning

confidence: 92%

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

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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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...

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Section: Course Of Sodiummentioning

confidence: 92%

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

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…While human cells are most desirable for forming anthropogenic RPE monolayers, the ethical issues and limited availability of human donors make culturing RPE cells from nonhuman animal donors a preferred alternative. RPE cells have been studied in nonhuman mammals, 33 , 62 , 139 – 141 birds, 1 , 142 and amphibians 44 , 115 , 128 and have been successfully harvested and cultured from several species of animals. 143 They have been grown in vitro for about as long as people have been culturing human RPE, 144 and many of the protocols established for human cells are also suitable for the cultivation of animal RPE.…”

Section: Cells Obtained From Tissuementioning

confidence: 99%

Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

Fronk

Vargis

2016

J Tissue Eng

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The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

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“…A normal FAF pattern reflects that the complex photoreceptor/RPE is working normally. FAF abnormalities are a common way to evaluate retinal changes in different states including aging, retinal detachment, toxicity and degenerative diseases (Baek et al, 2015;Issa et al, 2012;Secondi et al, 2012). Another wavelength is the near infrared light of 790 nm laser; this light induces FAF originating from melanin in the RPE and choroid (Gibbs et al, 2009;Keilhauer and Delori, 2006;Schmitz-Valckenberg et al, 2011), providing different patterns and alterations that those acquired with the 488 nm light.…”

Section: Introductionmentioning

confidence: 99%

Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence

Pinilla

Fernández‐Sánchez

Segura

et al. 2016

Experimental Eye Research

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We provide for the first time a detailed long-term analysis of the course of retinal degeneration in P23H rats using a combination of SLO and OCT imaging, angiography, FAF and IHC. Although, the application of noninvasive methods enables longitudinal studies and will decrease the number of animals needed for a study, IHC is still an essential tool to identify retinal changes at the cellular level.

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Fundus autofluorescence (FAF) non-invasively identifies chorioretinal toxicity in a rat model of retinal pigment epithelium (RPE) damage

Cited by 12 publications

References 27 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

Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence

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