Transplantation of the RPE in AMD

Binder, Susanne; Stanzel, Boris V.; Krebs, Ilse; Glittenberg, Carl

doi:10.1016/j.preteyeres.2007.02.002

Cited by 259 publications

(208 citation statements)

References 460 publications

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“…[1][2][3][4] This retinal degenerative disease affects the retinal pigment epithelium (RPE), the Bruch's membrane (BM), and the choroid, consequently leading to the damage of the photoreceptors. 1,2 The RPE constitutes the outer blood-retina barrier, preventing the transport of molecules larger than 300 kDa into and out of the retina. 5,6 Apically facing the photoreceptors and basolaterally the BM, RPE is a cell monolayer responsible for several complex functions essential for the visual function.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Cellulose As a Support for the Growth of Retinal Pigment Epithelium

Gonçalves¹,

Padrão²,

Rodrigues

et al. 2015

Biomacromolecules

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The feasibility of bacterial cellulose (BC) as a novel substrate for retinal pigment epithelium (RPE) culture was evaluated. Thin (41.6 ± 2.2 μm of average thickness) and heat-dried BC substrates were surface-modified via acetylation and polysaccharide adsorption, using chitosan and carboxymethyl cellulose. All substrates were characterized according to their surface chemistry, wettability, energy, topography, and also regarding their permeability, dimensional stability, mechanical properties, and endotoxin content. Then, their ability to promote RPE cell adhesion and proliferation in vitro was assessed. All surface-modified BC substrates presented similar permeation coefficients with solutes of up to 300 kDa. Acetylation of BC decreased it's swelling and the amount of endotoxins. Surface modification of BC greatly enhanced the adhesion and proliferation of RPE cells. All samples showed similar stress-strain behavior; BC and acetylated BC showed the highest elastic modulus, but the latter exhibited a slightly smaller tensile strength and elongation at break as compared to pristine BC. Although similar proliferation rates were observed among the modified substrates, the acetylated ones showed higher initial cell adhesion. This difference may be mainly due to the moderately hydrophilic surface obtained after acetylation. 2 ABSTRACT: The feasibility of bacterial cellulose (BC) as a novel substrate for retinal pigment epithelium (RPE) culture was evaluated. Thin (41.6 ± 2.2 µm of average thickness) and heatdried BC substrates were surface modified via acetylation and polysaccharide adsorption using chitosan and carboxymethyl cellulose. The BC substrates were characterized according to surface chemistry, wettability, energy, topography, permeability, dimensional stability, mechanical properties and level of endotoxins present. Then, the ability to promote RPE cell adhesion and proliferation in vitro was assessed. BC substrates were porous and permeable to solutes up to 300 kDa. The acetylation decreased substrate swelling and the amount of endotoxins present. Surface modification greatly enhanced the adhesion and proliferation of RPE cells in BC. Although similar proliferation rates were observed between the modified substrates, the acetylated ones showed higher initial cell adhesion. This difference may be mainly due to the moderately hydrophilic surface obtained after acetylation.

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Section: Introductionmentioning

confidence: 99%

Bacterial Cellulose As a Support for the Growth of Retinal Pigment Epithelium

Gonçalves¹,

Padrão²,

Rodrigues

et al. 2015

Biomacromolecules

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“…23 Physiological RPE cells are mitotically quiescent, with cell-cell contact inhibition mediated by the homotypic adhesion of cadherins on adjacent cells. 52 In the late phase of AMD, RPE dissociation can occur because of RPE and retinal detachment subsequent to CNV formation. 1 Once these contacts are disrupted and exposed by profibrotic growth factors (ie, TGF-b and PDGF), RPE cells undergo EMT.…”

Section: Discussionmentioning

confidence: 99%

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Ishikawa

Sreekumar

Spee

et al. 2016

The American Journal of Pathology

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Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial-mesenchymal transition (EMT) of retinal pigment epithelium cells. aB-crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of aB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in aB-crystallin knockout mice compared with wild-type mice. aB-crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of aB-crystallin induced EMT, whereas suppression of aB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-b2einduced EMT was further enhanced by overexpression of aB-crystallin but was inhibited by suppression of aB-crystallin. Silencing of aB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 upregulated aB-crystallin, and its EMT induction was inhibited by knockdown of aB-crystallin. Furthermore, inhibition of aB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of aB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, aB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration. (Am J Pathol 2016, 186: 859e873; http:// dx

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“…Recent work demonstrated the existence of endogenous, stem cell-like populations in adult heart, liver, brain, and kidney (33)(34)(35)(36)(37)(38)(39) . These resident stem cells may possess growth factor receptors that can be activated to induce their migration and proliferation and promote both the restoration of dead tissue and the improved function in damaged tissue.…”

Section: B5) Activation Of Neighboring Resident Stem Cellsmentioning

confidence: 99%

“…RPE dysfunction has been linked to many devastating eye disorders, including age-related macular degeneration, and to hereditary disorders, such as Stargardt disease and retinitis pigmentosa (38)(39)(40) . Attempts to repair the RPE include transplantation of RPE cells into the subretinal space (39)(40)(41)(42)(43)(44) .…”

Section: C) Retinal Pigment Epithelium (Rpe) Repair With Bm Derived Smentioning

confidence: 99%