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1.
Am J Transplant ; 24(9): 1583-1596, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38648890

RESUMO

The activation of innate immunity following transplantation has been identified as a crucial factor in allograft inflammation and rejection. However, the role of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling-mediated innate immunity in the pathogenesis of allograft rejection remains unclear. Utilizing a well-established murine model of corneal transplantation, we demonstrated increased expression of cGAS and STING in rejected-corneal allografts compared with syngeneic (Syn) and normal (Nor) corneas, along with significant activation of the cGAS/STING pathway, as evidenced by the enhanced phosphorylation of TANK-binding kinase 1and interferon regulatory factor 3. Pharmacological and genetic inhibition of cGAS/STING signaling markedly delayed corneal transplantation rejection, resulting in prolonged survival time and reduced inflammatory infiltration. Furthermore, we observed an increase in the formation of neutrophil extracellular traps (NETs) in rejected allografts, and the inhibition of NET formation through targeting peptidylarginine deiminase 4 and DNase I treatment significantly alleviated immune rejection and reduced cGAS/STING signaling activity. Conversely, subconjunctival injection of NETs accelerated corneal transplantation rejection and enhanced the activation of the cGAS/STING pathway. Collectively, these findings demonstrate that NETs contribute to the exacerbation of allograft rejection via cGAS/STING signaling, highlighting the targeting of the NETs/cGAS/STING signaling pathway as a potential strategy for prolonging allograft survival.


Assuntos
Transplante de Córnea , Armadilhas Extracelulares , Rejeição de Enxerto , Nucleotidiltransferases , Transdução de Sinais , Animais , Masculino , Camundongos , Aloenxertos , Armadilhas Extracelulares/metabolismo , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto/imunologia , Imunidade Inata , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética
2.
Am J Transplant ; 24(9): 1597-1609, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38514014

RESUMO

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10. Additionally, MDSC maintain forkhead box P3 stability and their ability to suppress IFN-γ+ Th1 cells. Administering MDSC to HR corneal transplant recipients demonstrates prolonged graft survival via promotion of Treg while concurrently suppressing IFN-γ+ Th1 cells. Moreover, MDSC-mediated donor-specific immune tolerance leads to long-term corneal graft survival as evidenced by the higher survival rate or delayed survival of a second-party C57BL/7 (B6) graft compared to those of third-party C3H grafts observed in contralateral low-risk or HR corneal transplantation of BALB/c recipient mice, respectively. Our study provides compelling preliminary evidence demonstrating the effectiveness of MDSC in preventing Treg dysfunction, significantly improving graft survival in HR corneal transplantation, and showing promising potential for immune tolerance induction.


Assuntos
Transplante de Córnea , Rejeição de Enxerto , Sobrevivência de Enxerto , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides , Linfócitos T Reguladores , Animais , Linfócitos T Reguladores/imunologia , Células Supressoras Mieloides/imunologia , Camundongos , Sobrevivência de Enxerto/imunologia , Rejeição de Enxerto/imunologia , Camundongos Endogâmicos C3H , Aloenxertos , Tolerância Imunológica/imunologia , Masculino
3.
Ophthalmology ; 131(6): 674-681, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38160881

RESUMO

PURPOSE: To compare the outcomes of deep anterior lamellar keratoplasty (DALK) using dehydrated versus standard organ culture-stored donor corneas for eyes with keratoconus. DESIGN: Prospective, randomized, single-center trial conducted in Italy. PARTICIPANTS: Adult patients (age ≥ 18 years) with keratoconus scheduled for elective DALK. METHODS: Patients undergoing successful type 1 bubble pneumatic dissection using a standard DALK technique were randomized during surgery to receive either dehydrated (n = 30) or standard organ culture-stored (n = 30) donor corneas. MAIN OUTCOME MEASURES: The primary study outcome was best spectacle-corrected visual acuity (BSCVA) 12 months after surgery. Secondary outcomes were refractive astigmatism (RA), endothelial cell density (ECD), and complication rates. RESULTS: Postoperative BSCVA did not significantly differ between groups at both time points: mean difference at 6 months was 0.030 logarithm of the minimum angle of resolution (logMAR; 95% confidence interval [CI], -0.53 to 0.10 logMAR; P = 0.471) and at 12 months was -0.013 logMAR (95% CI, -0.10 to 0.08 logMAR; P = 0.764). No significant differences between groups were observed in terms of postoperative RA and ECD at all time points. In the first 3 days after DALK, an epithelial defect was present in 10 patients (33%) in the organ culture cornea group and in 29 patients (97%) in the dehydrated cornea group. Complete re-epithelialization was achieved by day 7 in all patients (100%) in both groups. CONCLUSIONS: The study provides evidence that the use of dehydrated corneas is noninferior to the use of standard organ culture donor corneas for DALK. Corneal tissue dehydration represents a viable solution that can allow long-term cornea preservation and avoid wastage of unused corneas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Transplante de Córnea , Ceratocone , Técnicas de Cultura de Órgãos , Preservação de Órgãos , Doadores de Tecidos , Acuidade Visual , Humanos , Estudos Prospectivos , Masculino , Feminino , Adulto , Transplante de Córnea/métodos , Acuidade Visual/fisiologia , Ceratocone/cirurgia , Ceratocone/fisiopatologia , Preservação de Órgãos/métodos , Pessoa de Meia-Idade , Endotélio Corneano/patologia , Adulto Jovem , Córnea/cirurgia , Contagem de Células
4.
Exp Eye Res ; 242: 109857, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479724

RESUMO

Penetrating keratoplasty remains the most common treatment to restore vision for corneal diseases. Immune rejection after corneal transplantation is one of the major causes of graft failure. In recent years, Rho-associated protein kinase (ROCK) inhibitors have been found to be associated with the activation of the STATs pathway and are widely studied in autoimmune diseases. Therefore, it may be possible that the ROCK inhibitors also participate in the local and systemic immune regulation in corneal transplantation through activation of the STATs pathway and affect the CD4+ T cell differentiation. This study aimed to explore the role of ROCK-STATs pathway in the occurrence of immune rejection in corneal transplantation by applying Y27632, a ROCK inhibitor, to the recipient mice and peripheral CD4+ T cells. We found that Y27632 significantly up-regulated the phosphorylation level of STAT5 in both spleen and lymph nodes, down-regulated the phosphorylation level of STAT3 in the CD4+ T cells in the spleen. It also increased the proportion of CD4+CD25+Foxp3+Helios+ Tregs while decreased CD4+IL17A+ -Th17 cells. Moreover, Y27632 also reduced the proportion of dendritic cells in both spleen and lymph nodes, as well as the expression level of CD86 on their surfaces in the spleen, while the proportion of macrophages was not affected. The expression levels of ROCK1, ROCK2, CD11c and IL-17A mRNA were also found to be low in the graft tissue while the expression of Helios was upregulated. Rho-kinase inhibitor can modulate the balance of Tregs/Th17 by regulating the phosphorylation levels of both STAT3 and STAT5, thereby inhibiting the occurrence of immune rejection in allogeneic corneal transplantation.


Assuntos
Amidas , Linfócitos T CD4-Positivos , Rejeição de Enxerto , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Piridinas , Fator de Transcrição STAT3 , Fator de Transcrição STAT5 , Quinases Associadas a rho , Animais , Camundongos , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/prevenção & controle , Quinases Associadas a rho/antagonistas & inibidores , Linfócitos T CD4-Positivos/imunologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Amidas/farmacologia , Amidas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Modelos Animais de Doenças , Fosforilação , Citometria de Fluxo , Ceratoplastia Penetrante , Western Blotting , Transplante de Córnea , Masculino
5.
Graefes Arch Clin Exp Ophthalmol ; 262(4): 1195-1202, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37930442

RESUMO

PURPOSE: The purpose of this study is to determine the incidence of suture-related complications, their risk factors, and effects on the clinical outcomes after deep anterior lamellar keratoplasty (DALK) for keratoconus. METHODS: In this retrospective, comparative, interventional study, the records of consecutive patients with keratoconus who underwent DALK were reviewed for suture-related complications. Univariate analyses were used to identify risk factors for suture complications. We compared groups with and without suture-related complications to evaluate the effects of these complications on clinical outcomes after DALK. RESULTS: Of the 633 DALKs, 438 eyes (69.2%) developed suture complications including loose sutures (32.7%), spontaneous suture rupture (30%), sterile suture abscesses (22.8%), suture tract vascularization (16.4%), suture erosion (10.3%), and suture cheese wiring (6.8%). Vernal keratoconjunctivitis increased the incidence of sterile suture infiltration, premature suture loosening, and suture tract vascularization. Loose suture was observed more commonly in larger graft size, while spontaneous suture rupture was associated with late suture removal. There was no statistically significant difference in postoperative outcomes including visual acuity, refraction, graft rejection, and failure in eyes with and without suture complications. However, suture-related complications were directly associated with sight-threatening ocular morbidities, including graft rejection (39 eyes), ulcer (1 eye), and failure (2 eyes). CONCLUSION: Suture-related complications frequently occurred after DALK for keratoconus. Ocular surface inflammation, large grafts, and late suture removal increased the risk of suture-related complications. While these complications had no negative impact on clinical outcomes in the majority of cases, some of them led to sight-threatening morbidity, underlining the importance of early diagnosis and treatment.


Assuntos
Transplante de Córnea , Ceratocone , Humanos , Ceratocone/diagnóstico , Ceratocone/cirurgia , Ceratoplastia Penetrante/efeitos adversos , Transplante de Córnea/efeitos adversos , Estudos Retrospectivos , Refração Ocular , Suturas/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Seguimentos
6.
BMC Ophthalmol ; 24(1): 413, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334104

RESUMO

BACKGROUND: This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021. METHODS: The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty. RESULTS: The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002). CONCLUSIONS: The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.


Assuntos
Doenças da Córnea , Transplante de Córnea , Humanos , Estudos Retrospectivos , China/epidemiologia , Transplante de Córnea/métodos , Masculino , Feminino , Doenças da Córnea/cirurgia , Pessoa de Meia-Idade , Adulto , Centros de Atenção Terciária/estatística & dados numéricos , Idoso , Adolescente , Criança , Adulto Jovem , Pré-Escolar
7.
BMC Ophthalmol ; 24(1): 234, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831303

RESUMO

BACKGROUND: Ochrobactrum anthropi is widely distributed and primarily infects patients with compromised immune functions . Historically, O. anthropi has been considered to possess low toxicity and pathogenicity; however, recent studies suggest that it may in fact cause severe purulent infections. In this case study, we examine a case of O. anthropi infection following corneal transplantation, exploring the occurrence and outcomes of such post-operative infections. CASE PRESENTATION: A retrospective analysis of cases involved examinations, genetic testing for diagnosis, and subsequent treatment. In patients undergoing partial penetrating keratoplasty with a fungal corneal ulcer perforation, anterior chamber exudation and purulence were observed post-surgery. Despite antifungal treatment, genetic testing of the anterior chamber fluid and purulent material confirmed O. anthropi infection. The use of antimicrobial treatment specifically targeting O. anthropi was found to be effective in treating the infection. CONCLUSION: Inflammatory reactions following corneal transplantation should be should be monitored for the presence of other infections. Genetic testing has significant implications for clinical diagnosis and treatment.


Assuntos
Infecções Oculares Bacterianas , Infecções por Bactérias Gram-Negativas , Ochrobactrum anthropi , Humanos , Ochrobactrum anthropi/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/etiologia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/etiologia , Masculino , Ceratoplastia Penetrante/efeitos adversos , Úlcera da Córnea/microbiologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/etiologia , Transplante de Córnea/efeitos adversos , Feminino , Pessoa de Meia-Idade , Antifúngicos/uso terapêutico
8.
Cell Tissue Bank ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212857

RESUMO

Bowman's layer is an acellular corneal structure, which is considered to be a specially modified anterior stroma. It is presumed, that it forms as a result of ongoing epithelial-stromal interactions and no clear physiological purpose has been proven. Despite this fact, Bowman's layer has found its place in corneal transplantation. It has been performed for over a decade, mainly in treatment of advanced keratoconus with multiple modifications. Transplantation of Bowman's layer can be expected to become a widely used surgical procedure in the treatment of many corneal pathologies involving fragmentation and destruction of Bowman's layer. This article aims to summarize information available on its structure, possible function, and transplantation. A thorough literature search was performed in the PubMed database and Google Scholar using keywords: Bowman's layer, structure, function, preparation and corneal transplantation. All the relevant sources were used, which represent 77 peer-reviewed articles with information corcerning the topic of this article.

9.
Cell Tissue Bank ; 25(2): 619-623, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38141131

RESUMO

The cornea transplant is considered the most frequently performed type of transplant in the world, with a demand that has been increasing in recent years. An observational descriptive study was conducted, focusing on the ocular tissue extracted from cadaveric donors from January 2019 to December 2021 at the Red Cross Eye Bank in Medellin, Colombia. This is the first epidemiological characterization of corneal donor tissues within the eye banks of our city, where high rates of violence-related deaths explain that tissue donors are mostly young individuals. This, in turn, results in excellent counts of endothelial cells and tissue viability in their microscopic studies. Additionally, there are lower rates of discarded tissues compared to similar studies.


Assuntos
Córnea , Transplante de Córnea , Bancos de Olhos , Doadores de Tecidos , Colômbia , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Bancos de Olhos/estatística & dados numéricos , Idoso , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Cidades
10.
Int Ophthalmol ; 44(1): 230, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805103

RESUMO

PURPOSE: The present study aimed to epidemiologically evaluate patients with infectious keratitis following corneal transplantation. METHODS: This retrospective study analyzed medical records of patients who underwent keratoplasty from March 2014 to March 2022 at a tertiary center. A total of seventy-five patients were evaluated. The data were classified based on culture results, the type of microorganisms involved, treatment requirements, and the type of primary keratoplasty performed. RESULTS: Seventy-five patients were evaluated in this study, with a mean age of 45.9 years (22-95 years). The mean duration between the first surgery and the incidence of infectious keratitis was 1.43 years, and most cases occurred in the first year (56.2%). Bacterial and fungal keratitis in 2.17%, 1.39%, and 1.26% of cases undergoing penetrating keratoplasty (PK), endothelial keratoplasty (EK), and anterior lamellar keratoplasty (ALK) occurred, respectively. Streptococcus viridans (9.3%) and Staphylococcus aureus (6.6%) had the highest prevalence. Across various smear and culture results (gram-positive, gram-negative, fungal, and negative culture), no significant differences were found in endophthalmitis rates (P = 0.797) and the necessity for tectonic grafts (P = 0.790). Similarly, the choice of surgical method (PK, ALK, EK) showed no significant impact on the need for tectonic grafts (P = 0.45) or the rate of endophthalmitis (P = 0.55). CONCLUSIONS: The incidence of keratitis after a corneal graft was 1.7%, with Streptococcus viridans and Staphylococcus aureus the most common microorganisms. The rate of endophthalmitis associated with post-keratoplasty keratitis was 0.053%. There was no correlation between the necessity for a tectonic graft or the incidence of endophthalmitis and the type of microorganisms involved.


Assuntos
Transplante de Córnea , Infecções Oculares Bacterianas , Infecções Oculares Fúngicas , Ceratite , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/etiologia , Infecções Oculares Bacterianas/diagnóstico , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem , Idoso de 80 Anos ou mais , Incidência , Ceratite/epidemiologia , Ceratite/microbiologia , Ceratite/diagnóstico , Ceratite/etiologia , Transplante de Córnea/efeitos adversos , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/etiologia , Bactérias/isolamento & purificação , Complicações Pós-Operatórias/epidemiologia
11.
Int Ophthalmol ; 44(1): 289, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937283

RESUMO

PURPOSE: To evaluate the impact of an educational video in improving awareness of eye donation among non-medical healthcare workers at a tertiary health centre. METHODS: A socio-behavioural study on knowledge and attitude towards eye donation was conducted among 373 non-medical healthcare workers through a printed semi-structured questionnaire before and after viewing a bilingual educational video. The responses were evaluated and scored. RESULTS: Pre-intervention, only 5.4% of the participants had adequate knowledge, which improved significantly to 71.6% after watching the video (P < .001). Respondents with elementary school education showed the greatest change in knowledge. Pre-intervention, 72.4% were willing to donate their eyes, which significantly increased to 89.5% after watching the video. Pre-intervention, 66.22% showed a "highly favourable" attitude, which improved to 97.86% after watching the video. CONCLUSION: The 25 min video about eye donation and eye banking significantly changed the participants' knowledge, willingness, and attitude. Hence, media-based (video) awareness platforms may be valuable for improving the general public's knowledge and attitude towards eye donation. This may help in enhancing the eye donation rate in the long term.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Centros de Atenção Terciária , Obtenção de Tecidos e Órgãos , Humanos , Masculino , Feminino , Adulto , Inquéritos e Questionários , Obtenção de Tecidos e Órgãos/métodos , Pessoal de Saúde/educação , Pessoa de Meia-Idade , Adulto Jovem , Doadores de Tecidos/psicologia , Gravação em Vídeo , Educação em Saúde/métodos
12.
Vestn Oftalmol ; 140(1): 36-44, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38450465

RESUMO

PURPOSE: This study evaluates the long-term results of surgical treatment of patients with Fuchs' endothelial corneal dystrophy and cataract. MATERIAL AND METHODS: The study included 24 patients (24 eyes) with primary Fuchs' endothelial corneal dystrophy and cataract, who underwent cataract phacoemulsification with IOL implantation and of Descemet's membrane endothelial keratoplasty with a semicircular graft (hemi-DMEK). The effect of treatment was assessed by best corrected visual acuity (BCVA), central corneal thickness (CCT) and endothelial cell density (ECD). RESULTS: In total, surgical treatment involved 14 donor corneas that were divided in half during the preparation and isolation of the Descemet's membrane (DM). By month 12 after the surgery an increase in visual functions and graft transparency were observed in 23 patients (23 eyes) out of 24. Repeated keratoplasty was required in one case due to fibrosis of the posterior layers of recipient's corneal stroma. At 12 months postoperatively, the study group showed an increase in BCVA from 0.16±0.1 to 0.75±20, a decrease in CCT from 650.9±4.5 µm to 519.6±43.9, and a decreased in ECD from 2850.5±84.7 cells/mm2 up to 1285.5±277.2 cells/mm2. Thus, the loss of endothelial cells at one year after surgery amounted to 54.9%. CONCLUSIONS: The developed method for transplantation of a semicircular DM fragment provides a tissue-saving approach to endothelial keratoplasty, and considering the high percentage of transparent engraftment of grafts and complete visual rehabilitation, it can be recommended in the treatment of patients with cataract and Fuchs' endothelial corneal dystrophy.


Assuntos
Catarata , Transplante de Córnea , Distrofia Endotelial de Fuchs , Facoemulsificação , Humanos , Lâmina Limitante Posterior/cirurgia , Células Endoteliais , Catarata/complicações , Catarata/diagnóstico , Distrofia Endotelial de Fuchs/complicações , Distrofia Endotelial de Fuchs/diagnóstico , Distrofia Endotelial de Fuchs/cirurgia , Córnea
13.
J Proteome Res ; 22(12): 3730-3741, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976471

RESUMO

Cornea transplantation is one of the most commonly performed allotransplantations worldwide. Prolonged storage of donor corneas leads to decreased endothelial cell viability, severe stromal edema, and opacification, significantly compromising the success rate of corneal transplantation. Corneal stroma, which constitutes the majority of the cornea, plays a crucial role in maintaining its shape and transparency. In this study, we conducted proteomic analysis of corneal stroma preserved in Optisol-GS medium at 4 °C for 7 or 14 days to investigate molecular changes during storage. Among 1923 identified proteins, 1634 were quantifiable and 387 were significantly regulated with longer preservation. Compared to stroma preserved for 7 days, proteins involved in ocular surface immunomodulation were largely downregulated while proteins associated with extracellular matrix reorganization and fibrosis were upregulated in those preserved for 14 days. The increase in extracellular matrix structural proteins together with upregulation of growth factor signaling implies the occurrence of stromal fibrosis, which may compromise tissue clarity and cause vision impairments. This study is the first to provide insights into how storage duration affects corneal stroma from a proteomic perspective. Our findings may contribute to future research efforts aimed at developing long-term preservation techniques and improving the quality of preserved corneas, thus maximizing their clinical application.


Assuntos
Criopreservação , Proteômica , Humanos , Criopreservação/métodos , Córnea , Substância Própria/metabolismo , Matriz Extracelular , Gentamicinas/metabolismo , Misturas Complexas/metabolismo
14.
Am J Transplant ; 23(9): 1345-1358, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37245642

RESUMO

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lepob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.


Assuntos
Transplante de Córnea , Diabetes Mellitus Experimental , Animais , Camundongos , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Experimental/patologia , Estreptozocina , Córnea , Células Apresentadoras de Antígenos
15.
Exp Eye Res ; 230: 109457, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36948439

RESUMO

Corneal endothelial decompensation (CED) is the major cause of the long-term graft failure, but the underlying mechanisms remain unclear. The purpose of this study was to characterize the proteomic profile in CED aqueous humor (AH) after penetrating keratoplasty (PKP). We collected AH samples (n = 6/group) from CED patients underwent PKP and cataract patients, respectively. The label-free quantitative proteomic analysis was performed to identify the differentially-expressed proteins (DEPs). The biological functions of DEPs were evaluated using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis. The protein-protein interaction (PPI) network construction was employed to distinguish the hub proteins of DEPs, and the selected proteins were validated by parallel reaction monitoring (PRM). The human peripheral blood mononuclear cells (PBMCs) were adopted to investigate the effect of biglycan (BGN) on inflammatory response, and the subsequent outcomes of inflammation on human corneal endothelial cells (HCECs). A total of 174 DEPs were identified in CED AH of patients underwent PKP, including 102 up-regulated proteins and 72 down-regulated proteins. Bioinformatics analysis revealed the significant enrichment of cytokine-mediated signaling pathway and extracellular matrix (ECM) organization in the up-regulated proteins, as well as the alterations of cellular components, including the increase of collagen and complement component C1 complex, and reduction in extracellular exosomes. A hub protein cluster of 15 proteins was determined by Molecular Complex Detection (MCODE), including FN1, BGN, COMP, COL11A1, COLA3A1, and COL1A1. Moreover, BGN promoted pro-inflammatory cytokine (such as TNF-α, IL-1ß and IL-6) production in PBMCs through NF-κB signaling pathway, which subsequently resulted in HCECs death. These findings provided a systemic protein profile of AH in CED patients after corneal transplantation, with the alterations implicated in cytokine-mediated signaling, ECM, complement system, and exsomes. The identified proteins and signaling pathways probably paved the novel insight into understanding the pathogenesis of the disease.


Assuntos
Doenças da Córnea , Ceratoplastia Penetrante , Humanos , Humor Aquoso/metabolismo , Proteômica , Células Endoteliais , Leucócitos Mononucleares , Doenças da Córnea/metabolismo , Citocinas/metabolismo
16.
Graefes Arch Clin Exp Ophthalmol ; 261(6): 1619-1625, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36629951

RESUMO

PURPOSE: To investigate the potential role of keratometry on whole globes in situ of deceased patients by assessing its repeatability and comparing it with sterile donor tomography after excision and preservation in organ culture. METHODS: A sequence of 5 measurements was taken from 40 eyes in situ of deceased patients < 24 h after death using the portable Retinomax K-plus 3 (Bon, Tokyo, Japan). Keratometry of whole globes in situ, from which sclerocorneal discs were taken for organ culture, was compared to those obtained after measuring these sclerocorneal disks through their cell culture flask in medium I after 5 ± 4 days using the anterior segment optical coherence tomograph Casia 2 (Tomey Corp., Nagoya, Japan), and to 964 different donor corneas in medium II. RESULTS: Cronbach's alpha of the in situ keratometry was 0.891 and 0.942 for the steepest and flattest corneal power (P). The steepest (44.5D) and flattest (41.1D) P as well as the astigmatism (3.4D) of in situ corneas remained unchanged after preserving sclerocorneal discs in medium I (respectively 44.7D [p = 0.09]; 41.4D [p = 0.17]; 3.3D [p = 0.09]). The comparison of the in situ values with the 964 measured different donor corneas in medium II showed significantly (p < 0.001) higher P at the steep (45.4D) and flat (43.9D) meridian and smaller astigmatism (1.4D) for sterile donor tomography. CONCLUSIONS: Measuring deceased patients' eyes in situ with the portable Retinomax K-plus 3 represents a feasible and reliably repeatable screening method in the eye bank. In comparison to donor tomography in medium I, it measures a similar power and astigmatism.


Assuntos
Astigmatismo , Doenças da Córnea , Humanos , Bancos de Olhos , Astigmatismo/diagnóstico , Córnea , Doenças da Córnea/diagnóstico , Doenças da Córnea/cirurgia , Tomografia de Coerência Óptica/métodos , Topografia da Córnea/métodos
17.
BMC Ophthalmol ; 23(1): 408, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817122

RESUMO

PURPOSE: To report indications and clinical outcomes of corneal grafts ≤ 5.5 mm in diameter ("mini-KP") in a German tertiary referral center. METHODS: Patients who had undergone mini-KP to treat corneal ulcers with or without perforation between 2011 and 2018 at the Department of Ophthalmology, University of Düsseldorf, Germany, were identified from the local keratoplasty registry. All patient records were reviewed for age, gender, laterality, systemic and ophthalmological diseases, etiology of the corneal ulcerative disease, pre- and postoperative visual acuity over a follow-up time of up to 12 months, graft size, postoperative complications and the need for and timing of further corneal interventions. RESULTS: 37 eyes of 37 patients (male: n = 20; female: n = 17) with a mean age (± standard deviation) at presentation of 70 ± 18.8 years (range: 22-92 years) were identified. Most common etiologies were neurotrophic keratopathy (n = 15), dysfunctional tear syndrome (n = 9) and atopic keratoconjunctivitis (9). Mean graft diameter was 4.51 ± 0.63 mm (range: 3-5.5 mm). 23/37 eyes (62%) required no further intervention in the acute phase. 14/37 patients (38%) required secondary corneal intervention, due to complications. One-year graft survival was 78.4%. One eye had to be eviscerated due to recurrent corneal ulceration and endophthalmitis. 36 of 37 eyes were preserved. We found a highly significant correlation between type 2 diabetes and the development of postoperative complications (r = .46; p = .005). Corrected distance visual acuity (CDVA) improved from 1.42 ± 0.75 logMAR to 0.9 ± 0.65 logMAR postoperatively (t (23) = 5.76; p < .001). CONCLUSION: Mini-KP can be used successfully in eyes with advanced corneal ulcers due to various infectious and noninfectious etiologies to restore tectonic stability in the long-term and with moderate visual gains.


Assuntos
Doenças da Córnea , Distrofias Hereditárias da Córnea , Transplante de Córnea , Úlcera da Córnea , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Lactente , Ceratoplastia Penetrante , Úlcera/cirurgia , Doenças da Córnea/cirurgia , Úlcera da Córnea/cirurgia , Distrofias Hereditárias da Córnea/cirurgia , Complicações Pós-Operatórias/cirurgia , Sobrevivência de Enxerto , Estudos Retrospectivos , Resultado do Tratamento
18.
Med J Armed Forces India ; 79(6): 645-650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37981925

RESUMO

Corneal diseases are a major cause of blindness in the world. Corneal transplantation has been a cornerstone in the management of several of these advanced pathologies. This article discusses the evolution of corneal transplantation over a century, its indications, complications and briefly the various surgical techniques. Such tremendous technical improvisations from total corneal transplantation to lamellar keratoplasties have generated significant interest in the ophthalmic world and garnered momentum to the fight against blindness. Armed Forces Medical Services are also in vogue more than ever in this forward surge.

19.
Vestn Oftalmol ; 139(3): 90-97, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37379114

RESUMO

Pterygium is among the most frequent indications for extraocular ophthalmic surgery. The main method of pterygium treatment - its excision - is often combined with transplantation, non-transplantation, medication and other methods. However, the frequency of pterygium recurrence can exceed 35%, and the cosmetic and refraction outcomes satisfy neither the patient, nor the surgeon. PURPOSE: The study analyses the technical capability and feasibility for transplantation of the Bowman's layer in the treatment of recurrent pterygium. MATERIAL AND METHODS: The transplantation of the Bowmen's layer was performed according to the developed technique on 7 eyes with recurrent pterygium (7 patients aged 34 to 63 years). The combined surgery technique consisted of pterygium resection, laser ablation, autoconjunctival plasty, exposure to a cytostatic drug, non-suture transplantation of the Bowman's layer. Maximum length of the follow-up was 36 months. Analysis involved data from refractometry, visometry (without correction and with spectacle correction), and optical coherence tomography of the retina. RESULTS: There were no complications in any of the studied cases. The cornea and the transplant retained transparency throughout the entire follow-up duration. 36 months after surgery mean spectacle-corrected visual acuity amounted to 0.86±0.2, topographic astigmatism - 1.48±1.4 diopters. Recurrence of pterygium was not observed. All patients were satisfied with the cosmetic outcomes of the treatment. CONCLUSION: Non-suture transplantation of the Bowmen's layer recovers normal anatomy, physiology and transparency of the cornea after repeat surgical intervention for pterygium. No pterygium recurrences were observed throughout the entire follow-up after treatment with the proposed combined technique.


Assuntos
Pterígio , Humanos , Acuidade Visual , Pterígio/diagnóstico , Pterígio/etiologia , Pterígio/cirurgia , Córnea/cirurgia , Refração Ocular , Recidiva
20.
Vestn Oftalmol ; 139(2): 108-112, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37067940

RESUMO

Selective exchange of pathologically altered retinal layers is currently considered the most practical approach in corneal transplantation. Deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK) are often performed as pathogenetically substantiated transplantation methods. The technique and the course of surgery, possible complications, and achieved outcomes, among other things, depend largely on the pre-Descemet's layer, which was described more than 10 years ago by several ophthalmologists in varying detail. In view of this, the main issue discussed in literature is the following: is the pre-Descemet's layer (Dua's layer) a separate (new) layer of the cornea, or is it an integral part of the stroma (the Feizi stroma)? This article continues the discussion on «separate designation of the pre-Descemet's layer in the structure of the cornea¼ and presents the view of the authors on this problem based on own experience, literature data, anatomical subdisciplines, as well as specific aspects of ophthalmological terminology, and with the use of extrapolation and analogies.


Assuntos
Transplante de Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Córnea/cirurgia , Transplante de Córnea/métodos , Coleta de Tecidos e Órgãos
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