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  1. Article ; Online: Corneal Xenotransplantation: Anterior Lamellar Keratoplasty.

    Vabres, Bertrand / Vanhove, Bernard / Blancho, Gilles

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2110, Page(s) 245–251

    Abstract: Corneal transplantation for the treatment of corneal blindness is challenging in many countries due to the shortage of graft procurement. Xenocorneal transplantation is an interesting alternative to explore despite immunologic rejection, which mainly ... ...

    Abstract Corneal transplantation for the treatment of corneal blindness is challenging in many countries due to the shortage of graft procurement. Xenocorneal transplantation is an interesting alternative to explore despite immunologic rejection, which mainly involves endothelial cells. As anterior lamellar keratoplasty, when indicated, shows less immunologic reaction, we developed and describe below a pig-to-non-human-primate model of anterior lamellar corneal xenograft. This model can be used to assess the efficacy of corneas from genetically modified pigs.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Corneal Diseases/etiology ; Corneal Diseases/surgery ; Corneal Transplantation/adverse effects ; Corneal Transplantation/methods ; Graft Survival/immunology ; Heterografts ; Macaca fascicularis ; Male ; Postoperative Care ; Swine ; Transplantation, Heterologous/adverse effects ; Transplantation, Heterologous/methods
    Language English
    Publishing date 2020-01-30
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0255-3_16
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  2. Article ; Online: Comment on Descemet Stripping Endothelial Keratoplasty in Pediatric Patients with Congenital Hereditary Endothelial Dystrophy.

    Martin, Gilles C / Vabres, Bertrand / Dureau, Pascal / Lebranchu, Pierre / Caputo, Georges / Gabison, Eric

    American journal of ophthalmology

    2020  Volume 215, Page(s) 155

    MeSH term(s) Child ; Descemet Stripping Endothelial Keratoplasty ; Endothelium, Corneal ; Fuchs' Endothelial Dystrophy/surgery ; Humans ; Iridocorneal Endothelial Syndrome
    Language English
    Publishing date 2020-04-28
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80030-2
    ISSN 1879-1891 ; 0002-9394
    ISSN (online) 1879-1891
    ISSN 0002-9394
    DOI 10.1016/j.ajo.2020.02.027
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  3. Article: Keratoconus and the Impact of Treatment on Patients' Quality of Life: A Qualitative Study.

    Fournié, Pierre / Acquadro, Michaël / Touboul, David / Cochener, Béatrice / Chiambaretta, Frédéric / Muraine, Marc / Borderie, Vincent / Bourges, Jean-Louis / Benmedjahed, Khadra / Tugaut, Béatrice / Bernheim, Diane / Bourcier, Tristan / Burillon, Carole / David, Thierry / Delbosc, Bernard / Gain, Philippe / Hoffart, Louis / Labetoulle, Marc / Laroche, Laurent /
    Malet, Florence / Orignac, Isabelle / Robert, Pierre-Yves / Thuret, Gilles / Vabres, Bertrand / Malecaze, François / Arnould, Benoit

    Ophthalmology and therapy

    2023  Volume 12, Issue 4, Page(s) 1939–1956

    Abstract: Introduction: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment.: Methods: ...

    Abstract Introduction: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment.
    Methods: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes.
    Results: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL.
    Conclusions: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.
    Language English
    Publishing date 2023-05-08
    Publishing country England
    Document type Journal Article
    ISSN 2193-8245
    ISSN 2193-8245
    DOI 10.1007/s40123-023-00717-w
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  4. Article ; Online: Peripheral blood immune cell profiling of acute corneal transplant rejection.

    Hjortdal, Jesper / Griffin, Matthew D / Cadoux, Marion / Armitage, W John / Bylesjo, Max / Gabhann, Peadar Mac / Murphy, Conor C / Pleyer, Uwe / Tole, Derek / Vabres, Bertrand / Walkinshaw, Malcolm D / Gourraud, Pierre-Antoine / Karakachoff, Matilde / Brouard, Sophie / Degauque, Nicolas

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2022  Volume 22, Issue 10, Page(s) 2337–2347

    Abstract: Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were ... ...

    Abstract Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically diagnosed AR of full-thickness (FT)-CT (n = 35) and posterior lamellar (PL)-CT (n = 21) along with Stable CT recipients (n = 177) and adults with non-transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high-dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4
    MeSH term(s) Adult ; Corneal Transplantation ; Cross-Sectional Studies ; Graft Rejection/diagnosis ; Graft Rejection/etiology ; Graft Survival ; Humans ; Leukocytes, Mononuclear
    Language English
    Publishing date 2022-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.17119
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  5. Article ; Online: Exploration of the ocular surface infection by SARS-CoV-2 and implications for corneal donation: An ex vivo study.

    Maurin, Corantin / He, Zhiguo / Mentek, Marielle / Verhoeven, Paul / Pillet, Sylvie / Bourlet, Thomas / Rogues, Françoise / Pugniet, Jean Loup / Peyragrosse, Thierry / Barallon, Marion / Perrache, Chantal / Aouimeur, Inès / Acquart, Sophie / Ninotta, Sandrine / Baud'huin, Marc / Vabres, Bertrand / Poinard, Sylvain / Gain, Philippe / Thuret, Gilles

    PLoS medicine

    2022  Volume 19, Issue 3, Page(s) e1003922

    Abstract: Background: The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission through corneal graft is an ongoing debate and leads to strict restrictions in corneas procurement, leading to a major decrease in eye banking activity. ... ...

    Abstract Background: The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission through corneal graft is an ongoing debate and leads to strict restrictions in corneas procurement, leading to a major decrease in eye banking activity. The aims of this study are to specifically assess the capacity of human cornea to be infected by SARS-CoV-2 and promote its replication ex vivo, and to evaluate the real-life risk of corneal contamination by detecting SARS-CoV-2 RNA in corneas retrieved in donors diagnosed with Coronavirus Disease 2019 (COVID-19) and nonaffected donors.
    Methods and findings: To assess the capacity of human cornea to be infected by SARS-CoV-2, the expression pattern of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE-2) and activators TMPRSS2 and Cathepsins B and L in ocular surface tissues from nonaffected donors was explored by immunohistochemistry (n = 10 corneas, 78 ± 11 years, 40% female) and qPCR (n = 5 corneas, 80 ± 12 years, 40% female). Additionally, 5 freshly excised corneas (80 ± 12 years, 40% female) were infected ex vivo with highly concentrated SARS-CoV-2 solution (106 median tissue culture infectious dose (TCID50)/mL). Viral RNA was extracted from tissues and culture media and quantified by reverse transcription quantitative PCR (RT-qPCR) (viral RNA copies) 30 minutes (H0) and 24 hours (H24) after infection. To assess the risk of corneal contamination by SARS-CoV-2, viral RNA was tested by RT-qPCR (Ct value) in both corneas and organ culture media from 14 donors diagnosed with COVID-19 (74 ± 10 years, 29% female) and 26 healthy donors (79 ± 13 years, 57% female), and in organ culture media only from 133 consecutive nonaffected donors from 2 eye banks (73 ± 13 years, 29% female). The expression of receptor and activators was variable among samples at both protein and mRNA level. Based on immunohistochemistry findings, ACE-2 was localized mainly in the most superficial epithelial cells of peripheral cornea, limbus, and conjunctiva, whereas TMPRSS2 was mostly expressed in all layers of bulbar conjunctiva. A significant increase in total and positive strands of IP4 RNA sequence (RdRp viral gene) was observed from 30 minutes to 24 hours postinfection in central cornea (1.1 × 108 [95% CI: 6.4 × 107 to 2.4 × 108] to 3.0 × 109 [1.4 × 109 to 5.3 × 109], p = 0.0039 and 2.2 × 107 [1.4 × 107 to 3.6 × 107] to 5.1 × 107 [2.9 × 107 to 7.5 × 107], p = 0.0117, respectively) and in corneoscleral rim (4.5 × 109 [2.7 × 109 to 9.6 × 109] to 3.9 × 1010 [2.6 × 1010 to 4.4 × 1010], p = 0.0039 and 3.1 × 108 [1.2 × 108 to 5.3 × 108] to 7.8 × 108 [3.9 × 108 to 9.9 × 108], p = 0.0391, respectively). Viral RNA copies in ex vivo corneas were highly variable from one donor to another. Finally, viral RNA was detected in 3 out of 28 corneas (11%) from donors diagnosed with COVID-19. All samples from the 159 nonaffected donors were negative for SARS-CoV-2 RNA. The main limitation of this study relates to the limited sample size, due to limited access to donors diagnosed with COVID-19 and concomitant decrease in the procurement corneas from nonaffected donors.
    Conclusions: In this study, we observed the expression of SARS-CoV-2 receptors and activators at the human ocular surface and a variable increase in viral RNA copies 24 hours after experimental infection of freshly excised human corneas. We also found viral RNA only in a very limited percentage of donors with positive nasopharyngeal PCR. The low rate of positivity in donors diagnosed with COVID-19 calls into question the utility of donor selection algorithms.
    Trial registration: Agence de la Biomédecine, PFS-20-011 https://www.agence-biomedecine.fr/.
    MeSH term(s) Adult ; Aged ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/complications ; Cathepsins/metabolism ; Chlorocebus aethiops ; Cornea/metabolism ; Cornea/virology ; Corneal Diseases/virology ; Culture Media ; Eye Infections, Viral/virology ; Female ; Humans ; Male ; Middle Aged ; Organ Culture Techniques ; RNA, Viral/metabolism ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/physiology ; Serine Endopeptidases/metabolism ; Vero Cells ; Virus Replication
    Chemical Substances Culture Media ; RNA, Viral ; Receptors, Coronavirus ; Cathepsins (EC 3.4.-) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2022-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2185925-5
    ISSN 1549-1676 ; 1549-1277
    ISSN (online) 1549-1676
    ISSN 1549-1277
    DOI 10.1371/journal.pmed.1003922
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  6. Article ; Online: Ocular sequelae of epidermal necrolysis: French national audit of practices, literature review and proposed management.

    Thorel, Dhyna / Ingen-Housz-Oro, Saskia / Benaïm, Daniel / Daien, Vincent / Gabison, Eric / Saunier, Valentine / Béral, Laurence / Touboul, David / Brémond-Gignac, Dominique / Robert, Matthieu / Vasseur, Robin / Royer, Gérard / Dereure, Olivier / Milpied, Brigitte / Bernier, Claire / Welfringer-Morin, Anne / Bodemer, Christine / Cordel, Nadège / Tauber, Marie /
    Burillon, Carole / Servant, Marion / Couret, Chloe / Vabres, Bertrand / Tétart, Florence / Cassagne, Myriam / Kuoch, Marie-Ange / Muraine, Marc / Delcampe, Agnès / Gueudry, Julie

    Orphanet journal of rare diseases

    2023  Volume 18, Issue 1, Page(s) 51

    Abstract: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known ...

    Abstract Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.
    MeSH term(s) Humans ; Stevens-Johnson Syndrome/complications ; Lubricant Eye Drops/therapeutic use ; Disease Progression ; Cyclosporine/therapeutic use ; Adrenal Cortex Hormones/therapeutic use
    Chemical Substances Lubricant Eye Drops ; Cyclosporine (83HN0GTJ6D) ; Adrenal Cortex Hormones
    Language English
    Publishing date 2023-03-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2225857-7
    ISSN 1750-1172 ; 1750-1172
    ISSN (online) 1750-1172
    ISSN 1750-1172
    DOI 10.1186/s13023-023-02616-6
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  7. Article ; Online: High-risk Corneal Transplantation: Recent Developments and Future Possibilities.

    Armitage, W John / Goodchild, Christine / Griffin, Matthew D / Gunn, David J / Hjortdal, Jesper / Lohan, Paul / Murphy, Conor C / Pleyer, Uwe / Ritter, Thomas / Tole, Derek M / Vabres, Bertrand

    Transplantation

    2019  Volume 103, Issue 12, Page(s) 2468–2478

    Abstract: Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic ... ...

    Abstract Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure, and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.
    MeSH term(s) Allografts ; Corneal Diseases/surgery ; Corneal Transplantation/adverse effects ; Graft Rejection/drug therapy ; Graft Rejection/immunology ; Graft Survival ; Humans ; Immunosuppressive Agents/therapeutic use ; Risk Factors
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2019-12-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000002938
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  8. Article: Eye loss by exogenous endophthalmitis following anti-tumor necrosis factor therapy: a report of 3 cases.

    Le Goff, Benoit / Vabres, Bertrand / Cochereau, Isabelle / Bouvard, Beatrice / Lamirel, Cedric / Maugars, Yves / Berthelot, Jean-Marie

    The Journal of rheumatology

    2009  Volume 36, Issue 1, Page(s) 202–203

    MeSH term(s) Adult ; Aged ; Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/drug therapy ; Endophthalmitis/chemically induced ; Female ; Humans ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/adverse effects
    Chemical Substances Antirheumatic Agents ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2009-01
    Publishing country Canada
    Document type Case Reports ; Letter
    ZDB-ID 194928-7
    ISSN 1499-2752 ; 0315-162X
    ISSN (online) 1499-2752
    ISSN 0315-162X
    DOI 10.3899/jrheum.080236
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  9. Article ; Online: The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of xenocorneal transplantation.

    Kim, Mee Kum / Choi, Hyuk Jin / Kwon, Ivo / Pierson, Richard N / Cooper, David K C / Soulillou, Jean-Paul / O'Connell, Philip J / Vabres, Bertrand / Maeda, Naoyuki / Hara, Hidetaka / Scobie, Linda / Gianello, Pierre / Takeuchi, Yasuhiro / Yamada, Kazuhiko / Hwang, Eung-Soo / Kim, Sang Joon / Park, Chung-Gyu

    Xenotransplantation

    2014  Volume 21, Issue 5, Page(s) 420–430

    Abstract: To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal ... ...

    Abstract To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal transplantation, and propose guidelines for conduct of clinical xenocorneal transplantation trials. These proposed guidelines are modeled on the published consensus statement of the International Xenotransplantation Association regarding recommended guidelines for conduct of clinical islet xenotransplantation. It is expected that this initial consensus statement will be revised over time in response to scientific advances in the field, and changes in the regulatory framework based on accumulating clinical experience.
    MeSH term(s) Animals ; Clinical Trials as Topic/ethics ; Clinical Trials as Topic/methods ; Clinical Trials as Topic/standards ; Corneal Transplantation/ethics ; Corneal Transplantation/methods ; Corneal Transplantation/standards ; Humans ; Informed Consent ; Patient Selection ; Swine ; Transplantation, Heterologous/ethics ; Transplantation, Heterologous/methods ; Transplantation, Heterologous/standards
    Language English
    Publishing date 2014-09-01
    Publishing country Denmark
    Document type Consensus Development Conference ; Journal Article ; Practice Guideline ; Research Support, Non-U.S. Gov't
    ZDB-ID 1236298-0
    ISSN 1399-3089 ; 0908-665X
    ISSN (online) 1399-3089
    ISSN 0908-665X
    DOI 10.1111/xen.12129
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  10. Article ; Online: hCTLA4-Ig transgene expression in keratocytes modulates rejection of corneal xenografts in a pig to non-human primate anterior lamellar keratoplasty model.

    Vabres, Bertrand / Le Bas-Bernardet, Stéphanie / Riochet, David / Chérel, Yan / Minault, David / Hervouet, Jérémy / Ducournau, Yvette / Moreau, Anne / Daguin, Véronique / Coulon, Flora / Pallier, Annaïck / Brouard, Sophie / Robson, Simon C / Nottle, Mark B / Cowan, Peter J / Venturi, Eric / Mermillod, Pascal / Brachet, Philippe / Galli, Cesare /
    Lagutina, Irina / Duchi, Roberto / Bach, Jean-Marie / Blancho, Gilles / Soulillou, Jean-Paul / Vanhove, Bernard

    Xenotransplantation

    2014  Volume 21, Issue 5, Page(s) 431–443

    Abstract: Background: Human corneal allografting is an established procedure to cure corneal blindness. However, a shortage of human donor corneas as well as compounding economic, cultural, and organizational reasons in many countries limit its widespread use. ... ...

    Abstract Background: Human corneal allografting is an established procedure to cure corneal blindness. However, a shortage of human donor corneas as well as compounding economic, cultural, and organizational reasons in many countries limit its widespread use. Artificial corneas as well as porcine corneal xenografts have been considered as possible alternatives. To date, all preclinical studies using de-cellularized pig corneas have shown encouraging graft survival results; however, relatively few studies have been conducted in pig to non-human primate (NHP) models, and particularly using genetically engineered donors.
    Methods: In this study, we assessed the potential benefit of using either hCTLA4-Ig transgenic or α1,3-Galactosyl Transferase (GT) Knock-Out (KO) plus transgenic hCD39/hCD55/hCD59/fucosyl-transferase pig lines in an anterior lamellar keratoplasty pig to NHP model.
    Results: Corneas from transgenic animals expressing hCTLA4-Ig under the transcriptional control of a neuron-specific enolase promoter showed transgene expression in corneal keratocytes of the stroma and expression was maintained after transplantation. Although a first acute rejection episode occurred in all animals during the second week post-keratoplasty, the median final rejection time was 70 days in the hCTLA4-Ig group vs. 21 days in the wild-type (WT) control group. In contrast, no benefit for corneal xenograft survival from the GTKO/transgenic pig line was found. At rejection, cell infiltration in hCTLA4Ig transgenic grafts was mainly composed of macrophages with fewer CD3+ CD4+ and CD79+ cells than in other types of grafts. Anti-donor xenoantibodies increased dramatically between days 9 and 14 post-surgery in all animals.
    Conclusions: Local expression of the hCTLA4-Ig transgene dampens rejection of xenogeneic corneal grafts in this pig-to-NHP lamellar keratoplasty model. The hCTLA4-Ig transgene seems to target T-cell responses without impacting humoral responses, the control of which would presumably require additional peripheral immunosuppression.
    MeSH term(s) Abatacept ; Animals ; Animals, Genetically Modified ; Biomarkers/metabolism ; Corneal Keratocytes/immunology ; Corneal Keratocytes/metabolism ; Corneal Transplantation/methods ; Graft Rejection/genetics ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft Survival/genetics ; Graft Survival/immunology ; Immunoconjugates/genetics ; Immunoconjugates/metabolism ; Macaca fascicularis ; Male ; Models, Animal ; Sus scrofa/genetics ; Transgenes ; Transplantation, Heterologous/methods
    Chemical Substances Biomarkers ; Immunoconjugates ; Abatacept (7D0YB67S97)
    Language English
    Publishing date 2014-09
    Publishing country Denmark
    Document type Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1236298-0
    ISSN 1399-3089 ; 0908-665X
    ISSN (online) 1399-3089
    ISSN 0908-665X
    DOI 10.1111/xen.12107
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