Systemic cyclosporin A in high failure risk, repeated corneal transplantation

Rumelt, Shimon; Bersudsky, Valery; Blum-Hareuveni, Tami; Rehany, Uri

doi:10.1136/bjo.86.9.988

Cited by 59 publications

(35 citation statements)

References 21 publications

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“…However the results are inconsistent. Some studies have demonstrated a beneficial effect, whereas others have failed to find any improvement in outcome [4][5][6][7][8][9]. Mainly because of its nephrotoxic effects, CsA has not become routine in clinical practise.…”

Section: Introductionmentioning

confidence: 92%

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival

Stanojlović

Schlickeiser

Appelt

et al. 2010

Graefes Arch Clin Exp Ophthalmol

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Section: Introductionmentioning

confidence: 92%

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival

Stanojlović

Schlickeiser

Appelt

et al. 2010

Graefes Arch Clin Exp Ophthalmol

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“…16) Current cyclosporine eye drops developed for clinical application were normally prepared with maize, castor or peanut oil, and the oil-based eye drops were likely to induce side effects including hyperaemia, blurred vision, pricking, burning sensation and pain in the eyes. 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.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Wang

Zhang

2015

Biological & Pharmaceutical Bulletin

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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...

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“…Systemic administration of CyA is an effective therapy for the corneal graft rejection and some eye disorders. However, the long term systemic administration of a relatively high dose of CyA may lead to the serious systemic adverse effects, such as hypertension, nephrotoxicity and hepatotoxicity (Algros et al, 2002;Rumelt et al, 2002). Topical ocular administration of CyA provides a good alternative to the systemic delivery.…”

Section: Introductionmentioning

confidence: 99%

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution

Shen

Deng

Jin

et al. 2010

International Journal of Pharmaceutics

102

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Systemic cyclosporin A in high failure risk, repeated corneal transplantation

Cited by 59 publications

References 21 publications

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival

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

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution

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