A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate

Monés, Jordi; Leiva, Marta; Peña, Teresa; Martı́nez, Gema; Biarnés, Marc; Garcia, Míriam; Serrano, A; Fernández, Eduardo

doi:10.1167/iovs.16-19355

Cited by 42 publications

(44 citation statements)

References 33 publications

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“…17,20 Recently, it was further shown that photoreceptors and RPE die through distinct mechanisms, the former through apoptosis and the latter through necroptosis. 21 In a swine model, subretinal blebs of NaIO 3 were shown to induce dose-dependent damage to the outer neuroretina and alterations to the RPE/Bruch's complex as shown by SD-OCT. 22 However, since BAF was not used in that study, a direct comparison at the RPE level with the present study cannot be done.…”

Section: Discussionmentioning

confidence: 79%

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy

Petrus‐Reurer

Bartuma

Aronsson

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Subretinal suspension transplants of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) have the capacity to form functional monolayers in naive eyes. We explore hESC-RPE integration when transplanted in suspension to a large-eyed model of geographic atrophy (GA).METHODS. Derivation of hESC-RPE was performed in a xeno-free and defined manner. Subretinal bleb injection of PBS or sodium iodate (NaIO 3 ) was used to induce a GA-like phenotype. Suspensions of hESC-RPE were transplanted to the subretinal space of naive or PBS-/NaIO 3 -treated rabbits using a transvitreal pars plana technique. Integration of hESC-RPE was monitored by multimodal real-time imaging and by immunohistochemistry.RESULTS. Subretinal blebs of PBS or NaIO 3 caused different degrees of outer neuroretinal degeneration, RPE hyperautofluorescence, focal RPE loss, and choroidal atrophy; that is, hallmark characteristics of GA. In nonpretreated naive eyes, hESC-RPE integrated as subretinal monolayers with preserved overlying photoreceptors, yet not in areas with outer neuroretinal degeneration and native RPE loss. When transplanted to eyes with PBS-/NaIO 3 -induced degeneration, hESC-RPE failed to integrate. CONCLUSIONS.In a large-eyed preclinical model, subretinal suspension transplants of hESC-RPE did not integrate in areas with GA-like degeneration.

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Section: Discussionmentioning

confidence: 79%

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy

Petrus‐Reurer

Bartuma

Aronsson

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Following stimulation with human vitreous or fibronectin, RPE cells differentiate and migrate to the vitreous body (12,13). RPE cells proliferate and secrete molecules into the extracellular matrix (ECM), resulting in formation of periretinal membrane with contraction ability, leading to retinal detachment (14,15). Inflammatory cytokines may be involved in ECM function and cell proliferation; therefore, it was hypothesized that inflammatory cytokines affect ECM, induce abnormal proliferation of RPE cells and contribute to the development of RRD (16,17).…”

Section: Introductionmentioning

confidence: 99%

IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment

Zhao

Wang

2018

Mol Med Report

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Rhegmatogenous retinal detachment (RRD) is a disorder of the eye that affects physical and mental health. Retinal pigment epithelium (RPE) is closely associated with RRD, and it is hypothesized that RPE-secreted inflammatory cytokines may induce early pathological changes of RRD and may participate in RPE proliferation and migration. The present study determined a role for interleukin (IL)‑10 as an RPE‑secreted immune regulatory factor that contributes to RRD. A rat RRD model was established and RPE cells were isolated and cultivated. RPE cells were randomly divided into four groups, three treated with different concentrations of IL‑10 (100, 50, and 20 mM) and one untreated. RPE cell proliferation was evaluated by MTT assay and the activity of caspase‑3 was also measured. RPE cell invasion was determined by Transwell assay. Vascular endothelial growth factor A (VEGF) expression was examined by reverse transcription‑quantitative polymerase chain reaction and western blotting; IL‑1 and IL‑6 levels were measured by ELISA. IL‑10 treatment suppressed RPE cell proliferation and migration, promoted caspase‑3 activity, inhibited VEGF mRNA and protein expression, and downregulated the secretion of inflammatory cytokines IL‑1 and IL‑6 in RRD group compared with the untreated Model group. The aforementioned effects of IL‑10 became more evident with increasing IL‑10 concentration. IL‑10 suppressed inflammation, facilitated RPE cell apoptosis and inhibited cell proliferation and migration through the regulation of VEGF expression.

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“…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. 13,23 Although a dysfunction of the RPE cells leads to a reduction in vision, 24 the time-dependent changes in the RPE morphological and physiological changes have not been determined.…”

mentioning

confidence: 99%

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

Moriguchi

Nakamura

Inoue

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate

Cited by 42 publications

References 33 publications

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy

IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment

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

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