A Novel 3D Cultured Model for Studying Early Changes in Age‐Related Macular Degeneration

Shokoohmand, Ali; Jeon, June; Theodoropoulos, Christina; Baldwin, Jeremy; Hutmacher, Dietmar W.; Feigl, Beatrix

doi:10.1002/mabi.201700221

Cited by 26 publications

(14 citation statements)

References 39 publications

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“…The current investigation is a preliminary research aimed at studying the involvement of integrins in RPEimmune cells interaction in AMD and the potential use of integrin antagonists within this frame. To confirm data obtained in the current study other in vitro cell culture models, including polarized human RPE cells (Khristov et al, 2018) and 3D cultured models (Forest et al, 2015;Shokoohmand et al, 2017;Schnichels et al, 2020) should be further employed. Animal models recapitulating several aspects of AMD are needed to further validate results obtained in vitro models.…”

Section: Discussionsupporting

confidence: 63%

Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration

et al. 2021

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Age-related macular degeneration (AMD) is a complex multifactorial degenerative disease that leads to irreversible blindness. AMD affects the macula, the central part of the retina responsible for sharp central vision. Retinal pigment epithelium (RPE) is the main cellular type affected in dry AMD. RPE cells form a monolayer between the choroid and the neuroretina and are in close functional relationship with photoreceptors; moreover, RPE cells are part of the blood retina barrier that is disrupted in ocular diseases such as AMD. During ocular inflammation lymphocytes and macrophages are recruited, contact RPE and produce pro-inflammatory cytokines, which play an important role in AMD pathogenesis. The interaction between RPE and immune cells is mediated by leukocyte integrins, heterodimeric transmembrane receptors, and adhesion molecules, including VCAM-1 and ICAM-1. Within this frame, this study aimed to characterize RPE-leukocytes interaction and to investigate any potentially beneficial effects induced by integrin antagonists (DS-70, MN27 and SR714), developed in previous studies. ARPE-19 cells were co-cultured for different incubation times with Jurkat cells and apoptosis and necrosis levels were analyzed by flow cytometry. Moreover, we measured the mRNA levels of the pro-inflammatory cytokine IL-1β and the expression of adhesion molecules VCAM-1 and ICAM-1. We found that RPE-lymphocyte interaction increased apoptosis and necrosis levels in RPE cells and the expression of IL-1β. This interaction was mediated by the binding of α4β1 and αLβ2 integrins to VCAM-1 and ICAM-1, respectively. The blockade of RPE-lymphocyte interaction with blocking antibodies highlighted the pivotal role played by integrins. Therefore, α4β1 and αLβ2 integrin antagonists were employed to disrupt RPE-lymphocyte crosstalk. Small molecule integrin antagonists proved to be effective in reducing RPE cell death and expression of IL-1β, demonstrating that integrin antagonists could protect RPE cells from detrimental effects induced by the interaction with immune cells recruited to the retina. Overall, the leukocyte integrin antagonists employed in the present study may represent a novel opportunity to develop new drugs to fight dry AMD.

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Section: Discussionsupporting

confidence: 63%

Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration

et al. 2021

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“…A PCL and gelatin electrospun, laminin coated membrane was described by Shokoohmand et al [ 37 ], to set up cell cocultures. Monkey choroidal endothelial cells (RF/6A) were first seeded on the bottom layer of the membrane, and after 6 days of culture, human RPE cells were seeded on the top layer.…”

Section: In Vitro Models Of Vamdmentioning

confidence: 99%

Experimental Models in Neovascular Age Related Macular Degeneration

Rastoin

Pagès

Dufies

2020

IJMS

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Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.

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“…This model includes choroidal fibroblasts with their endogenous ECM, as well as choroidal melanocytes [218], endothelial cells, and the retinal pigment epithelium, and successfully recaptures the biomechanical properties of the native tissue [219]. This innovative 3D system is superior to previously published in vitro models of the choroid, which used synthetic scaffolds or primate choroidal endothelial cells [220,221]. UM-like spheroids were also seeded in this tissue-engineered choroid model to decipher the pathological contribution of the choroidal microenvironment in UM progression [222] and to eventually provide a valuable tool to improve the treatment of the primary tumor.…”

Section: Uveal Melanomamentioning

confidence: 99%

Human Organ‐Specific 3D Cancer Models Produced by the Stromal Self‐Assembly Method of Tissue Engineering for the Study of Solid Tumors

Roy

Magne

Vaillancourt-Audet

et al. 2020

BioMed Research International

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Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.

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A Novel 3D Cultured Model for Studying Early Changes in Age‐Related Macular Degeneration

Cited by 26 publications

References 39 publications

Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration

Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration

Experimental Models in Neovascular Age Related Macular Degeneration

Human Organ‐Specific 3D Cancer Models Produced by the Stromal Self‐Assembly Method of Tissue Engineering for the Study of Solid Tumors

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