Rapamycin Inhibits Corneal Allograft Rejection and Neovascularization

Olsen, Timothy W.; Benegas, Nancy; Joplin, Andrea C.; Evangelista, Tony; Mindrup, Elizabeth A.; Holland, Edward J.

doi:10.1001/archopht.1994.01090230085026

Cited by 38 publications

(14 citation statements)

References 12 publications

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“…In rat experiments, Olsen et al found that rapamycin reduced the rejection of corneal allograft and neovascularization. 23 In an experimental model, rapamycin demonstrates no cellular toxicity at concentrations that suppress cell proliferation and regulate neovascularization. 24 In our present study, the modulating effects of rapamycin and bevacizumab on the wound-healing process following PRK were evaluated.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab and Rapamycin Can Decrease Corneal Opacity and Apoptotic Keratocyte Number following Photorefractive Keratectomy

Lee

Ko²,

Kim³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We investigated the effects of bevacizumab and rapamycin on central corneal opacity and apoptotic keratocyte number after photorefractive keratectomy (PRK) followed by ultraviolet B (UV-B) irradiation. METHODS.A total of 60 right eyes of Sprague-Dawley rats in four groups (n ¼ 15 each) underwent PRK ablation to 80 lm with a 3-mm zone. Sponges soaked with 0.02% mitomycin C (MMC), 2.5% bevacizumab, 0.01% rapamycin, and balanced saline solution were applied for 2 minutes to these eyes in the MMC, bevacizumab, rapamycin, and control groups, respectively. At 3 weeks after PRK, all right eyes were exposed to 100 mJ/cm 2 UV-B irradiation. Biomicroscopy was used to determine the amount of haze, and TUNEL staining for apoptosis and histology were performed at 3, 6, and 12 weeks.RESULTS. Contrary to the results at 3 weeks, central corneal haze, and apoptotic keratocyte and keratocyte number decreased significantly in the MMC, bevacizumab, and rapamycin groups compared to the control group, and the keratocyte number was lower in the MMC group than the bevacizumab and rapamycin groups at 6 weeks (all P < 0.05). At 12 weeks, the apoptotic keratocyte number was lower in the MMC, bevacizumab, and rapamycin groups than the control group, and the keratocyte number was significantly lower in the MMC than the rapamycin and control groups (all P < 0.05).CONCLUSIONS. Intraoperative bevacizumab and rapamycin administration decreases central corneal haze and apoptotic keratocyte number after PRK. Bevacizumab and rapamycin may be safe alternatives to MMC during refractive surgery to prevent postoperative corneal opacity less affecting the keratocyte number. (Invest Ophthalmol Vis Sci. 2012; 53:7645-7653)

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Section: Discussionmentioning

confidence: 99%

Bevacizumab and Rapamycin Can Decrease Corneal Opacity and Apoptotic Keratocyte Number following Photorefractive Keratectomy

Lee

Ko²,

Kim³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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show abstract

“…Campistol et al [27] reported the complete remission of Kaposi's sarcoma, which is associated with herpes virus 8, in 2 renal transplant recipients after switching from cyclosporine to rapamycin. Olsen et al [28] reported that the systemic administration of rapamycin prolongs corneal allograft survival and significantly inhibits the neovascular component of rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. However, it has been demonstrated that it does not permeate freshly isolated pig corneas [29] .…”

Section: Discussionmentioning

confidence: 99%

Prolongation of Corneal Allograft Survival by Topical Application of Everolimus in Experimental Keratoplasty

Li¹,

Büch

Otasevic³

et al. 2008

Ophthalmic Res

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Background: Everolimus is a novel proliferation signal inhibitor that has potent immunosuppressive activity. As previously shown, systemic administration of the drug could effectively enhance the mean survival time (MST) of corneal allografts. Commonly, the topical application of immunomodulatory agents is preferred over systemic use, in order to reduce the side effects. Purpose: To investigate the efficacy of topically applied everolimus to prevent corneal graft rejection in an experimental model. Methods: A total of 45 female Lewis rats received 3.5-mm grafts of MHCI/II incompatible Dark Agouti donors. Recipients were randomly assigned to receive either: (1) 0.05% everolimus microemulsion, (2) 0.025% everolimus microemulsion or (3) a vehicle as the control. Treatment was started on the day of surgery and applied 5 times daily. Grafts were graded every day and a rejection score was generated based on cornea clarity and oedema. Results: Local administration of 0.05 or 0.025% everolimus was effective in prolonging the mean survival time of corneal grafts (MST = 21 ± 6.57 days and 16.4 ± 2.3 days, respectively) as compared to vehicle control group (MST = 13.3 ± 1.7 days; p < 0.001 and p < 0.001). Real-time PCR demonstrated that topical administration of everolimus increased the mRNA levels of CD25, IL-10 and IFN-γ, but this was significant only for IL-10 (p = 0.015). Conclusions: These data indicate that topically applied everolimus is effective in prolonging corneal allograft survival in an experimental keratoplasty model.

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“…Therefore, it is important to determine the efficacy of RAPA in models of high-risk corneal rejection. Olsen et al 17 first reported the usefulness of RAPA in preventing corneal graft rejection in a rat model. Their treatment protocol relied on intramuscular injections.…”

Section: Discussionmentioning

confidence: 99%

Sustained Intraocular Rapamycin Delivery Effectively Prevents High-Risk Corneal Allograft Rejection and Neovascularization in Rabbits

Shi

Gao

Xie

et al. 2006

Invest. Ophthalmol. Vis. Sci.

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Rapamycin Inhibits Corneal Allograft Rejection and Neovascularization

Cited by 38 publications

References 12 publications

Bevacizumab and Rapamycin Can Decrease Corneal Opacity and Apoptotic Keratocyte Number following Photorefractive Keratectomy

Bevacizumab and Rapamycin Can Decrease Corneal Opacity and Apoptotic Keratocyte Number following Photorefractive Keratectomy

Prolongation of Corneal Allograft Survival by Topical Application of Everolimus in Experimental Keratoplasty

Sustained Intraocular Rapamycin Delivery Effectively Prevents High-Risk Corneal Allograft Rejection and Neovascularization in Rabbits

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