Co-cultivation of primary porcine RPE cells and neuroretina induces inflammation: a potential inflammatory AMD-model

Fietz, Agnes; Schnichels, Sven; Hurst, José

doi:10.1038/s41598-023-46029-8

Cited by 3 publications

(1 citation statement)

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“…At the boundary between in vitro and in vivo tests, ex vivo experiments may be performed. Fietz et al developed a model of a primary porcine RPE monolayer cocultured with porcine retinal organ cultures [114]. They found that this co-culture induced inflammation and could, therefore, be a reliable inflammatory AMD model.…”

Section: Representative Models Of Amd 61 In Vitro and Ex Vivo Modelsmentioning

confidence: 99%

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Brito,

Sorbier,

Mignet

et al. 2024

IJMS

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Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

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Section: Representative Models Of Amd 61 In Vitro and Ex Vivo Modelsmentioning

confidence: 99%

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Brito,

Sorbier,

Mignet

et al. 2024

IJMS

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Cytokine-Driven NF-κB Activation in Retinal Cells and Its Impact on the Pathogenesis of Age-Related Macular Degeneration: A Systematic Review

Shafi,

Khan,

Kazmi

et al. 2024

Preprint

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Objective: To investigate the role of cytokine-induced NF-κB activation in retinal pigment epithelium (RPE) and photoreceptor cells, elucidating its contribution to the pathogenesis of Age-related Macular Degeneration (AMD) and identifying potential therapeutic targets. Background: AMD is a leading cause of vision loss in older adults, driven by inflammation, oxidative stress, and immune dysregulation, particularly in RPE and photoreceptor cells. The NF-κB signaling pathway, activated by cytokines such as TNF-α, IL-6, and IL-1β, regulates these pathological processes. Understanding cytokine-induced NF-κB activation may provide insight into AMD progression and facilitate the development of novel therapeutic strategies. Methods: A systematic review of literature from databases including PubMed, MEDLINE, and Google Scholar was conducted to evaluate the involvement of TNF-α, IL-6, IL-1β, IL-8, IFN-γ, IL-17, IL-12, IL-18, IL-33, and IL-25 in activating NF-κB in RPE and photoreceptor cells, contributing to AMD pathogenesis. The search was performed with no date restrictions and followed PRISMA guidelines. Eligible studies were selected based on predefined criteria assessing NF-κB activation mechanisms and its effects on inflammation, oxidative stress, and retinal degeneration. Results: The investigation revealed that cytokines TNF-α, IL-6, IL-1β, IL-8, IFN-γ, IL-17, IL-12, IL-18, IL-33, and IL-25 activate the NF-κB signaling pathway in retinal pigment epithelium (RPE) and photoreceptor cells. This activation triggers the transcription of genes involved in inflammation, oxidative stress, and immune responses. Chronic NF-κB activation leads to persistent inflammation, increased oxidative stress, and immune cell recruitment, contributing to retinal cell dysfunction and degeneration. Additionally, NF-κB-driven upregulation of angiogenic factors such as VEGF promotes neovascularization in wet AMD. These findings highlight the central role of NF-κB in AMD pathogenesis and suggest that targeting this pathway could mitigate inflammatory and oxidative damage, offering potential therapeutic benefits for AMD patients. Conclusion: Cytokine-induced NF-κB activation plays a central role in AMD pathogenesis by promoting chronic inflammation, oxidative stress, and angiogenesis in retinal cells. Targeting NF-κB could present a therapeutic strategy to reduce inflammatory and oxidative damage, preserving retinal function and preventing vision loss in AMD. Further research is required to develop effective NF-κB-targeted interventions.

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Effects of mesenchymal stromal cells and human recombinant Nerve Growth Factor delivered by bioengineered human corneal lenticule on an innovative model of diabetic retinopathy

Pelusi,

Hurst,

Detta

et al. 2024

Front. Endocrinol.

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IntroductionDiabetic retinopathy (DR) is a microvascular complication of diabetes in which neurodegeneration has been recently identified as a driving force. In the last years, mesenchymal stromal cells (MSCs) and neurotrophins like Nerve Growth Factor (NGF), have garnered significant attention as innovative therapeutic approaches targeting DR-associated neurodegeneration. However, delivering neurotrophic factors directly in the eye remains a challenge. Hence, this study evaluated the effects of MSCs from human amniotic fluids (hAFSCs) and recombinant human NGF (rhNGF) delivered by human corneal lenticule (hCL) on a high glucose (HG) induced ex vivo model simulating the molecular mechanisms driving DR.MethodsPorcine neuroretinal explants exposed to HG (25 mM for four days) were used to mimic DR ex vivo. hCLs collected from donors undergoing refractive surgery were decellularized using 0.1% sodium dodecyl sulfate and then bioengineered with hAFSCs, microparticles loaded with rhNGF (rhNGF-PLGA-MPs), or both simultaneously. Immunofluorescence (IF) and scanning electron microscopy (SEM) analyses were performed to confirm the hCLs bioengineering process. To assess the effects of hAFSCs and rhNGF, bioengineered hCLs were co-cultured with HG-treated neuroretinal explants and following four days RT-PCR and cytokine array experiments for inflammatory, oxidative, apoptotic, angiogenic and retinal cells markers were performed.ResultsData revealed that HG-treated neuroretinal explants exhibit a characteristic DR-phenotype, including increased level of NF-kB, NOS2, NRF2 GFAP, VEGFA, Bax/Bcl2 ratio and decreased expression of TUBB3 and Rho. Then, the feasibility to bioengineer decellularized hCLs with hAFSCs and rhNGF was demonstrated. Interestingly, co-culturing hAFSCs- and rhNGF- bioengineered hCLs with HG-treated neuroretinal explants for four days significantly reduced the expression of inflammatory, oxidative, apoptotic, angiogenic and increased retinal markers.ConclusionOverall, we found for the first time that hAFSCs and rhNGF were able to modulate the molecular mechanisms involved in DR and that bioengineered hCLs represents a promising ocular drug delivery system of hAFSCs and rhNGF for eye diseases treatment. In addition, results demonstrated that porcine neuroretinal explants treated with HG is a useful model to reproduce ex vivo the DR pathophysiology.

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Co-cultivation of primary porcine RPE cells and neuroretina induces inflammation: a potential inflammatory AMD-model

Cited by 3 publications

References 68 publications

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Cytokine-Driven NF-κB Activation in Retinal Cells and Its Impact on the Pathogenesis of Age-Related Macular Degeneration: A Systematic Review

Effects of mesenchymal stromal cells and human recombinant Nerve Growth Factor delivered by bioengineered human corneal lenticule on an innovative model of diabetic retinopathy

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