Topical Cyclosporine in Corneal Transplantation

Ziaei, Mohammed; Manzouri, Bita

doi:10.1097/ico.0000000000000291

Cited by 26 publications

(29 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cyclosporine A (CsA) is one of the most promising immunosuppressive drugs and is widely used to prevent tissue rejection following organ transplantation [59]. CsA can be administered topically or by a subconjunctival injection to treat a variety of inflammatory disorders of the ocular surface [59–61].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13

et al. 2017

View full text Add to dashboard Cite

We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA. A scratch wound healing migration assay was performed to determine the effects of bevacizumab and/or CsA. Protein expression of both MMPs in pterygium tissues and in cells migrating from organ-cultured pterygium tissues was greater than that observed in normal cells. Inhibition of the activities of both MMPs decreased their expression levels; these were also significantly reduced in bevacizumab-injected pterygium tissues. Bevacizumab significantly reduced the expression of both MMPs and cell migration. Pretreatment with CsA prior to bevacizumab exposure markedly inhibited cell migration and the expression of both MMPs. CsA enhanced the inhibitory effects of bevacizumab on pterygium fibroblast migration in vitro, possibly by inhibiting expression of both MMPs. These findings suggest that combined CsA and bevacizumab treatment may provide a potential therapeutic strategy for reducing the rate of pterygium recurrence.

show abstract

Section: Introductionmentioning

confidence: 99%

“…CsA can be administered topically or by a subconjunctival injection to treat a variety of inflammatory disorders of the ocular surface [59–61]. CsA prevents the activation and nuclear translocation of cytoplasmic transcription factors that are required for T-helper cell activation and inflammatory cytokine production [62].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13

et al. 2017

View full text Add to dashboard Cite

show abstract

“…17) It is also reported that 2% oil based eye drop would possibly lead to corneal epithelial lesions. 9) To circumvent the drawbacks, we developed cyclosporine eye drops that were produced with nanophase materials. The drug was embedded within biodegradable nanomicelles that have high biocompatibility, which could significantly decrease the side effects.…”

Section: Discussionmentioning

confidence: 99%

“…8) It has been implied that cyclosporine might supress the expression of regulatory molecules related to the initiation of immune response. 9) Intracellular adhesion molecule 1 (ICAM-1) was identified as one of the risk factors involved in the development of transplantation rejection, and the inhibitory effects of cyclosporine on ICAM-1 expression were also revealed. 10) Though a growing body of evidences have revealed the therapeutic value of cyclosporine in the prevention and treatment of corneal transplantation rejection, 11) the mechanism by which cyclosporine might supress transplantation rejection and its effect on ICAM-1 expression remained elusive.…”

mentioning

confidence: 99%

Cyclosporine Nanomicelle Eye Drop: A Novel Medication for Corneal Graft Transplantation Treatment

Zhang

Wang

Zhang

2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Corneal transplantation has been used to treat severe eye disease for decades, but the therapeutic effect of the operation is highly compromised by immunological allograft rejection. To improve the success rate of corneal transplantation, we studied the protective effects of cyclosporine nanomicelle eye drops (CNED) on immune rejection after high-risk corneal transplantation and its underlying mechanisms. The therapeutic effects against immune rejection of both conventional cyclosporine eye drop (CCED) and CNED in different concentrations were assessed and compared using animal models of corneal transplantation. In addition, the expression of nuclear factor-κ-gene binding (NF-κB) as well as its target intracellular adhesion molecule 1 (ICAM-1) in the corneal samples obtained from recipients treated with either CCED or CNED was also screened. The results showed that the CNED displayed significantly better effects at suppressing the immune response induced by corneal transplantation compared to CCED. CNED also significantly down-regulated the NF-κB and ICAM-1 expressions, indicating NF-κB might play an important role in the initiation of an immune response against the allograft. Our study demonstrates CNED may suppress the NF-κB pathway to attenuate the immune response, which highlights the possible therapeutic applications of cyclosporine nanomicelle eye drops in corneal transplantation. Key words cyclosporine; nuclear factor-κ-gene binding (NF-κB); corneal allograft transplantation; intracellular adhesion molecule 1 (ICAM-1)Corneal transplantation is the most successful form of solid tissue grafting that serves as a crucial therapy in treating blindness clinically.1) Immunological allograft rejection is considered to be the leading cause of corneal graft failure. Though the 5-year survival rate of low-risk keratoplasty is approximately 90%, the survival rate of high-risk keratoplasty remains below 50% due to immune-mediated rejection even with maximal local immune suppression.2) The high-risk allograft host is characterized by vascularized and inflamed recipient beds, and the pre-existing corneal blood and lymphatic vessels in recipient beds were identified as the primary risk factors for immunological allograft rejection.3) Blood vessels circulates nutrients, oxygen and cells in blood vasculature while lymphatic vessels deliver antigenic materials and donor-derived antigen-presenting cells to the lymph nodes, subsequently inducing immune response against the corneal transplant. 4)Pharmacotherapy for corneal allograft rejection has considerably reduced the rate of graft failure. However, the therapeutic strategy based on corticosteroids remains unimproved over the past decades.5) Multiple side effects of corticosteroids have been observed including cataracts, glaucoma and opportunistic infections, and the EC 50 of the drug varies in either the prevention or the treatment of allograft rejection. 6) Considering the high failure rate of transplantation and the low efficiency of current treatment strategy, the devel...

show abstract

“…burning) associated with its application. For systemic CsA, hypertension, nephrotoxicity, hepatotoxicity, hirsuitism, gingival hyperplasia, neurotoxicity, sensory abnormalities and reactivation of latent tuberculosis have all been reported as a complication in high risk keratoplasty [46, 47]. Many of these complications are uncommon if the patient is appropriately screened before and monitored during therapy [43].…”

Section: Immunosuppressive Therapymentioning

confidence: 99%

Update on the Management of High-Risk Penetrating Keratoplasty

Jabbehdari

Rafii

Yazdanpanah

et al. 2017

Curr Ophthalmol Rep

View full text Add to dashboard Cite

Purpose of review In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Recent findings Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Summary Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

show abstract

Topical Cyclosporine in Corneal Transplantation

Cited by 26 publications

References 34 publications

Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13

Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13

Cyclosporine Nanomicelle Eye Drop: A Novel Medication for Corneal Graft Transplantation Treatment

Update on the Management of High-Risk Penetrating Keratoplasty

Contact Info

Product

Resources

About