Immune Cells on the Corneal Endothelium of an Allogeneic Corneal Transplantation Rabbit Model

Koudouna, Elena; Okumura, Naoki; Okazaki, Yugo; Nakano, Shinichiro; Inoue, Ryota; Fullwood, Nigel J.; Hori, Junko; Kinoshita, Shigeru; Koizumi, Noriko

doi:10.1167/iovs.16-20019

Cited by 22 publications

(15 citation statements)

References 33 publications

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“…In the setting of xenotransplantation, these features were consistent with acute graft rejection 33,34 . In keeping with this, small DIR positive cells, consistent with previous reports of in ammatory cells, were observed interspersed with the endothelial cells were seen in both in the rabbit endothelial monolayer and transplanted human endothelial cells 35 .…”

Section: Discussionsupporting

confidence: 92%

Near Infra-Red Labelling and Tracking of Transplanted Corneal Endothelial Graft

Bhogal

Ang

Lin

et al. 2021

Preprint

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Following corneal transplantation, there is an initial decline in corneal endothelial cells (CECs) following graft preparation and surgery. Monitoring post-transplantation is only possible months after surgery by specular microscopy, which has a limited field of view. We have developed a labelling approach using 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindotricarbocyanine iodide (DIR) dye solution, that enabled tracking of labelled CECs in vivo for at least one month. Initial in vitro optimization of dye concentration, cellular toxicity and real-time cell migration was assessed using propagated primary CECs. Subsequent in vivo evaluation of cellular labelling was assessed within a rabbit wound healing model. Finally, real-time visualization of human cadaver donor tissue incubated in DIR transplanted into rabbits was achieved using the Heidelberg Spectralis. Results revealed detectable fluorescence increased with concentration to a plateau of 100µg/ml, with no toxicity of CECs at any concentration evaluated. DIR-labelled CECs were detectable in vivo upto 1 month, and transplanted labelled donor graft could be visualized and were trackable in vivo. Acute endothelial rejection in 1 rabbit was evidenced by detectable DIR positive cells within the anterior chamber. DIR imaging allowed for detailed imaging of the transplanted corneal endothelium, and enabled non-invasive observation of the corneal endothelial morphology following transplantation.

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Section: Discussionsupporting

confidence: 92%

Near Infra-Red Labelling and Tracking of Transplanted Corneal Endothelial Graft

Bhogal

Ang

Lin

et al. 2021

Preprint

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“…During long-term observation, the corneas of the CEC-like cell group still maintained transparent and thickness, and there are no new precipitates or vessels appeared 36 . The HE and immunohistochemical staining also showed that there were little inflammatory cells in the cornea 37 . There might be three reasons.…”

Section: Discussionmentioning

confidence: 87%

Therapy of corneal endothelial dysfunction with corneal endothelial cell-like cells derived from skin-derived precursors

Shen

Sun

Zhang

et al. 2017

Sci Rep

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Corneal endothelial dysfunction occurs when corneal endothelial cells (CECs) are dramatically lost and eventually results in vision loss. Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors. Therefore, finding new functional CECs to replace human CECs is urgent. Skin-derived precursors (SKPs) can be easily acquired and have multiple differential potential. We co-cultured human SKPs with B4G12 cells in serum-free medium and obtained abundant CEC-like cells which had similar morphology and characteristic to human CECs. CEC-like cells exerted excellent therapeutic effect when they were transplanted into rabbit and monkey corneal endothelial dysfunction models by injection method. This protocol enables efficient production of CEC-like cells from SKPs. The renewable cell source, novel derivation method and simple treatment strategy may lead to potential applications in cell replacement therapy for corneal endothelial dysfunction.Corneal endothelial cells (CECs) are a monolayer of hexagonal cells covering the posterior surface of the cornea, and serve as a barrier between the corneal stroma and the aqueous humor. The tight junction as well as the ionic "pump" functions of CECs are important factors that maintain corneal transparency 1 . Many pathological factors such as trauma, surgery, and inflammation may cause dramatic loss of endothelial cell density, resulting in corneal endothelial dysfunction which is characterized by corneal edema, bullous keratopathy, and loss of visual acuity 2 . Human CECs have limited proliferative capacity in vivo and cannot be subcultured for more than a few passages in vitro 3,4 . Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors 5 . Therefore, finding new functional CECs to replace human CECs is a new and potential direction for future clinical application.Skin-derived precursors (SKPs) were discovered by Tomas 6,7 , and they have been a research hotspot in recent years. SKPs can be isolated in large quantities from many parts of the skin in rodents and humans. As they are multipotent, they can be differentiated into several functional cell types 8 , and are able to suppress the allogeneic activation of T-lymphocytes resulting in an improved health status of animals suffering from a graft-versus-host reaction 9 . Moreover, SKPs were demonstrated to be embryonic neural-crest-related precursors and share many properties with neural crest stem cells 10

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“…In Figure D, inflammatory cells (red‐dashed circles) were occasionally observed in the vicinity of the 3D‐BDCS. Nevertheless, T lymphocytes, which play a crucial role in cell‐mediated immunity , were not observed.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the implantation of patient‐specific 3D bioprinted corneas made of ECM components could replace existing treatments. Fabricated bioengineered corneal substitutes are generally evaluated using histologic examinations in experimental animal models . The fabricated cornea is implanted into the eye of an experimental animal for 2 or 4 weeks, and then the cornea of the animal is extracted and evaluated.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Park

Lee

Kim

et al. 2019

Journal of Biophotonics

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Corneal transplantation by full-thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas.Although corneal transplantation has a high success rate, a shortage of highquality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three-dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept-source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude-scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth-intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery. Jaeseok Park, Kyoung-Pil Lee and Hyeonji Kim contributed equally to this work.

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Immune Cells on the Corneal Endothelium of an Allogeneic Corneal Transplantation Rabbit Model

Cited by 22 publications

References 33 publications

Near Infra-Red Labelling and Tracking of Transplanted Corneal Endothelial Graft

Near Infra-Red Labelling and Tracking of Transplanted Corneal Endothelial Graft

Therapy of corneal endothelial dysfunction with corneal endothelial cell-like cells derived from skin-derived precursors

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

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