Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation
Abstract Introduction We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Methods Tear sam...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-01-01
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| Series: | Ophthalmology and Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s40123-023-00656-6 |
| _version_ | 1827985002167533568 |
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| author | Gustavo S. Figueiredo Jeffry Hogg Arthur Okonkwo Oliver J. Baylis Monica Berry Simi Ali Majlinda Lako Francisco C. Figueiredo |
| author_facet | Gustavo S. Figueiredo Jeffry Hogg Arthur Okonkwo Oliver J. Baylis Monica Berry Simi Ali Majlinda Lako Francisco C. Figueiredo |
| author_sort | Gustavo S. Figueiredo |
| collection | DOAJ |
| description | Abstract Introduction We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Methods Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer’s strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). Results IL1β expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1β, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. Conclusion IL1β is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1β, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. Trial Registration European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011—000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481). |
| first_indexed | 2024-04-09T23:07:53Z |
| format | Article |
| id | doaj.art-d0b2c15290dc4ad3a631d9375d0d28e3 |
| institution | Directory Open Access Journal |
| issn | 2193-8245 2193-6528 |
| language | English |
| last_indexed | 2024-04-09T23:07:53Z |
| publishDate | 2023-01-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Ophthalmology and Therapy |
| spelling | doaj.art-d0b2c15290dc4ad3a631d9375d0d28e32023-03-22T10:36:41ZengAdis, Springer HealthcareOphthalmology and Therapy2193-82452193-65282023-01-011221097110710.1007/s40123-023-00656-6Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell TransplantationGustavo S. Figueiredo0Jeffry Hogg1Arthur Okonkwo2Oliver J. Baylis3Monica Berry4Simi Ali5Majlinda Lako6Francisco C. Figueiredo7Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation TrustHH Wills Physics Laboratory, University of BristolInstitute of Cellular Medicine, Newcastle UniversityFaculty of Medical Sciences, Biosciences Institute, Newcastle UniversityDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation TrustAbstract Introduction We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Methods Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer’s strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). Results IL1β expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1β, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. Conclusion IL1β is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1β, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. Trial Registration European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011—000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481).https://doi.org/10.1007/s40123-023-00656-6Autologous limbal stem cell transplantCytokinesOcular surface inflammationLimbal stem cell deficiencyTears |
| spellingShingle | Gustavo S. Figueiredo Jeffry Hogg Arthur Okonkwo Oliver J. Baylis Monica Berry Simi Ali Majlinda Lako Francisco C. Figueiredo Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation Ophthalmology and Therapy Autologous limbal stem cell transplant Cytokines Ocular surface inflammation Limbal stem cell deficiency Tears |
| title | Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation |
| title_full | Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation |
| title_fullStr | Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation |
| title_full_unstemmed | Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation |
| title_short | Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation |
| title_sort | understanding ocular surface inflammation in tears before and after autologous cultivated limbal epithelial stem cell transplantation |
| topic | Autologous limbal stem cell transplant Cytokines Ocular surface inflammation Limbal stem cell deficiency Tears |
| url | https://doi.org/10.1007/s40123-023-00656-6 |
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