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News Article | May 1, 2017
Site: www.rdmag.com

A new strategy may increase the tolerance of corneal transplants in patients at high risk for rejection. Researchers from Massachusetts Eye and Ear have presented a new study that shows that by targeting antigen-presenting cells in donor tissues with a combination of two cytokines, TGF-β and IL-10 can work to promote tolerance of the graft by the transplant recipient’s immune system. “We made use of cytokines that can change the function of immune cells to induce tolerance in donor corneas,” senior author Dr. Reza Dana, director of Cornea and Refractive Surgery at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School, said in a statement. “We exposed donor tissue to a particular cocktail of immunoregulatory cytokines, and we've determined what doses, concentrations and exposure we need for these cytokines to generate tolerance inducing antigen-presenting cells in the cornea,” he added. The researchers developed the technique in preclinical models to make the donor tissue more likely to be accepted by the host, rather than tweaking the immune system of the host to accept the donated tissue. The researchers treated donor tissue with the TGF-β and IL-10 mixture and then grafted them onto high-risk recipient eyes of a preclinical model. After eight weeks’ post-transplant, the researchers saw that 68.7 percent of treated grafts had survived, while none of the control grafts had survived. There are more than 150,000 cases of corneal transplantation performed worldwide each year. The transplants are necessary when the cornea is no longer able to let light in due to scarring or disease. While many of these transplants are successful in restoring vision, about one-third of all cases are considered high-risk with an increased chance of rejecting even with the use of steroids to suppress the immune system. The patients who reject the transplant often show signs of a degeneration of what is known as T cell-immunity. According to the researchers, the new method along with a combination of cytokines could work towards promoting tolerance of corneal grafts and may transition more easily to the clinical setting. “By exposing the transplant tissue to these cytokines, we avoid having to expose the transplant recipients themselves to any immunosuppressive,” Dana said. “We're very excited, because it's highly translatable technology. “When we grafted the tissue that has been treated that way, we developed active tolerance, which leads to long-term acceptance of the corneal transplant and suppresses all the destructive sides of immunity,” he added. The study was published in Scientific Reports.

Shetty R.,Cornea and Refractive Surgery | Nuijts R.M.M.A.,Maastricht University | Srivatsa P.,Cornea and Refractive Surgery | Jayadev C.,Cornea and Refractive Surgery | And 3 more authors.
BioMed Research International | Year: 2015

Purpose. To evaluate correlation between tomographic gradation of keratoconus (KC) and its corresponding air-puff induced biomechanical response. Methods. Corneal tomography and biomechanics were measured with Scheimpflug imaging in 44 normal and 92 KC corneas. Deformation waveform was also analyzed with Fourier series. A custom KC severity scale was used from 1 to 3 with 3 as the most severe grade. Tomographic and biomechanical variables were assessed among the grades. Sensitivity and specificity of the variables were assessed using receiver operating characteristics (ROC). Results. Curvature variables were significantly different between normal and disease (P<0.05) and among grades (P<0.05). Biomechanical variables were significantly different between normal and disease (P<0.05) but similar among grades 1 and 2 (P>0.05). All variables had an area under the ROC curve greater than 0.5. The root mean square of the Fourier cosine coefficients had the best ROC (0.92, cut-off: 0.027, sensitivity: 83%, specificity: 88.6%). Spearman correlation coefficient was significant between most variables (P<0.05). However, tomographic segregation of keratoconus did not result in concomitant biomechanical segregation of the grades. Conclusions. There was lack of significant biomechanical difference between mild disease grades, despite progressive corneal thinning. Mathematical models that estimate corneal modulus from air-puff deformation may be more useful. © 2015 Rohit Shetty et al.

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