A Review of the Cytokine IL-17 in Ocular Surface and Corneal Disease

Garbutcheon-Singh, K B; Carnt, Nicole; Pattamatta, Ushasree; Samarawickrama, Chameen; White, Andrew; Calder, Virginia L.

doi:10.1080/02713683.2018.1519834

Cited by 17 publications

(9 citation statements)

References 82 publications

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“…Presence of IL-17a in corneal tissue has a role in its immune privilege and may be involved in allograft survival ( 67 , 68 ). However, IL-17a might indirectly support neutrophils survival and tissue infiltration in allo-transplantation settings ( 69 ). Activated neutrophils can trigger rejection by recruiting CD8+ T cells through FAS ligand expression.…”

Section: Discussionmentioning

confidence: 99%

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Valdivia¹,

Bertolin

Breda

et al. 2021

Front. Immunol.

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Limbal stem cell (LSC) transplantation is the only efficient treatment for patients affected by LSC deficiency (LSCD). Allogeneic LSC transplantation is one of the most successful alternative for patients with bilateral LSCD. Nevertheless, the high variability of the human leukocyte antigens (HLA) remains a relevant obstacle to long-term allogeneic graft survival. This study characterized the immunologic properties of LSCs and proposed a genetic engineering strategy to reduce the immunogenicity of LSCs and of their derivatives. Hence, LSC HLA expression was silenced using lentiviral vectors encoding for short hairpin (sh) RNAs targeting β2-microglobulin (β2M) or class II major histocompatibility complex transactivator (CIITA) to silence HLA class I and II respectively. Beside the constitutive expression of HLA class I, LSCs showed the capability to upregulate HLA class II expression under inflammatory conditions. Furthermore, LSCs demonstrated the capability to induce T-cell mediated immune responses. LSCs phenotypical and functional characteristics are not disturbed after genetic modification. However, HLA silenced LSC showed to prevent T cell activation, proliferation and cytotoxicity in comparison to fully HLA-expressing LSCs. Additionally; HLA-silenced LSCs were protected against antibody-mediated cellular-dependent cytotoxicity. Our data is a proof-of-concept of the feasibility to generate low immunogenic human LSCs without affecting their typical features. The use of low immunogenic LSCs may support for long-term survival of LSCs and their derivatives after allogeneic transplantation.

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Section: Discussionmentioning

confidence: 99%

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Valdivia¹,

Bertolin

Breda

et al. 2021

Front. Immunol.

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“…56,60 There is a large body of animal research that indicated IL-17 exacerbates severity in bacterial and fungal corneal infection but is protective in Acanthamoeba keratitis, but this has not been explored in humans. 62 This area of study remains at an early stage, and studies have been limited by the small sample sizes because of the low incidence of disease, such that in some studies CL-related and non-CL-related infectious keratitis and sterile keratitis cases are grouped together and ethnicity differences limit the interpretation of findings. As the field matures, meta-analyses may reveal a genetic risk profile for CL-related infectious keratitis and sterile infiltrates that adjusts for ethnicity.…”

Section: Geneticsmentioning

confidence: 99%

Epidemiology, Microbiology, and Genetics of Contact Lens–Related and Non–Contact Lens-Related Infectious Keratitis

Stapleton

Vijay

Carnt

2022

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non-CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CLrelated and non-CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity.

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“…Interleukin 17 (IL-17) plays an important role in a wide variety of immunological diseases, but on the ocular surface it promotes neutrophil infiltration in tissues that induce synthesis and secretion of matrix metalloproteinases and ROS that generate disruption in the corneal epithelium, loss of epithelial functionality and induction of apoptosis. This contributes to the induction of neovascularization with stimulation of proangiogenic factor and modulation of cytoskeleton, which was examined in the vitreous and plasma of patients with DR, with levels significantly increased in PDR [114,206,207].…”

Section: Inflammation: Cytokines and Relevance In Drmentioning

confidence: 99%

Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy

et al. 2020

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Diabetic retinopathy is one of the leading causes of visual impairment and morbidity worldwide, being the number one cause of blindness in people between 27 and 75 years old. It is estimated that ~191 million people will be diagnosed with this microvascular complication by 2030. Its pathogenesis is due to alterations in the retinal microvasculature as a result of a high concentration of glucose in the blood for a long time which generates numerous molecular changes like oxidative stress. Therefore, this narrative review aims to approach various biomarkers associated with the development of diabetic retinopathy. Focusing on the molecules showing promise as detection tools, among them we consider markers of oxidative stress (TAC, LPO, MDA, 4-HNE, SOD, GPx, and catalase), inflammation (IL-6, IL-1ß, IL-8, IL-10, IL-17A, TNF-α, and MMPs), apoptosis (NF-kB, cyt-c, and caspases), and recently those that have to do with epigenetic modifications, their measurement in different biological matrices obtained from the eye, including importance, obtaining process, handling, and storage of these matrices in order to have the ability to detect the disease in its early stages.

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A Review of the Cytokine IL-17 in Ocular Surface and Corneal Disease

Abstract: IL-17 plays a role in the pathogenesis of ocular surface and corneal disease and targeting this cytokine may provide a useful treatment option in the future.

Cited by 17 publications

References 82 publications

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

Epidemiology, Microbiology, and Genetics of Contact Lens–Related and Non–Contact Lens-Related Infectious Keratitis

Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy

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