Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose

García-Delgado, Ana Belén; Cerda, Berta de la; Amador, Julia Alba; Sánchez, Maria Lourdes Valdés; Fernández‐Muñoz, Beatriz; Relimpio-López, María Isabel; Rúa, Enrique Rodríguez de la; Lloret, Andrea Díez; Pernaute, Rosario Sánchez; Bhattacharya, Shom Shanker; Corrales, Francisco Javier Díaz

doi:10.1089/ten.tea.2019.0007

Cited by 18 publications

(7 citation statements)

References 29 publications

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“…Twenty-six studies reported ERG data. Fourteen [46,[52][53][54][55][56][57][58][59][60][61][62][63][64] of them were excluded from meta-analysis since they did not report quantitative data or only showed single representative ERG traces.…”

Section: A-wave and B-wave Amplitudes Extracted From Erg Datamentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

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The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used. Methods: In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a-and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. Results: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave Int.(Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 5 versus in the range o...

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Section: A-wave and B-wave Amplitudes Extracted From Erg Datamentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Some advocate using 20 G 17 – 19 or 17 G device 7 ; other investigators altered an intraocular lens inserter. 20 , 21 Those instruments are still considered to be a large devices in the era of microincision vitrectomy surgery. For example, Kamao et al 17 used a fluid flow path with a 20 G catheter to guide the RPE monolayer into the subretinal space.…”

Section: Discussionmentioning

confidence: 99%

Methodological Approach to Improve Surgical Outcomes of a Pig Subretinal Implantation Model

Mano

Gandhi

Silva

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose To improve outcomes for subretinal implantation surgery in pigs. Methods Analysis of variables affecting the success of subretinal implantation surgery was performed on videos of 37 surgeries. Ex vivo experiments were conducted to measure intraocular pressure (IOP) and test various prototyped implanters for effectiveness at maintaining IOP. Results A video analysis revealed a prolonged sclerotomy open time owing to a combination of uncontrolled bleeding and excessive fluid outflow often resulting in retinal prolapse. Precauterization of the choroid before full-thickness sclerotomy ( n = 10) resulted in a reduced incidence of uncontrolled bleeding from 39.1% (9/23) versus 0% (0/10) ( P = 0.005) and improved implantation success from 73% to 90%. An ex vivo analysis of the IOP revealed a mean decrease in the IOP from 30.2 ± 3.0 mm Hg to 5.0 ± 2.1 mm Hg after a fully penetrating sclerotomy. To address this situation, we produced a series of plugs that integrated with a custom implant insertion device to seal the sclerotomy during implantation. The use of the plugs was cumbersome, however, and so we opted instead to increase the width of the inserter tip to fill the open sclerotomy. This improved device restored and maintained IOP during implantation (27.1 ± 1.9 mm Hg). Combined with precauterization the improved inserter resulted in 100% successful implantation ( n = 4). Conclusions For subretinal implantation in pigs, a modified procedure to precauterize the choroid before sclerotomy combined with an instrument that better fills the scleral opening decreases bleeding, hypotony, and open sclerotomy time, improving the success rate. Translational Relevance Better management of IOP and bleeding from a sclerotomy will improve implant-based therapies.

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“…Moreover, hydrogels have a similar structure to the natural extracellular matrix (ECM) and contain a large amount of water, which allows for a suitable microenvironment to encapsulate cells, drugs, and biomolecules [ 6 , 7 , 8 , 9 , 10 ]. Examples of hydrogels used in retinal TE include hyaluronic acid (HA) [ 11 , 12 , 13 , 14 , 15 , 16 ], methyl (MC) [ 15 , 16 ], gellan gum (GG) [ 17 , 18 , 19 ], alginate (Alg) [ 2 , 20 , 21 ], agarose (Ag) [ 22 , 23 ], gelatin (Gel) [ 14 , 19 , 24 , 25 ], fibrinogen [ 23 , 26 , 27 , 28 ], poly (ethylene glycol) (PEG) [ 18 , 21 , 29 , 30 ], and poly- l -lysine (PLL) [ 13 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells

et al. 2022

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Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.

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Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose

Cited by 18 publications

References 29 publications

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Methodological Approach to Improve Surgical Outcomes of a Pig Subretinal Implantation Model

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells

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