Development of a completely encapsulated intraocular pressure sensor.

A completely encapsulated intraocular pressure (IOP) sensor equipped with telemetric signal and energy transfer is introduced integrated into a silicone disc for implantation into the eye. After implantation into enucleated pig eyes and into rabbit eyes in vivo, the IOP was recorded and compared to established techniques of IOP measurement. Pressure chamber tests showed that the sensor functioned correctly after biocompatible encapsulation in polydimethylsiloxane. In vivo and in vitro tests in rabbit and pig eyes demonstrated that the implanted system worked with the same precision as established techniques for IOP determination. The correlation between the measurements with the implanted device and pneumotonometry in several experiments was between 0.9 and 0.99. This device serves as a functioning model for the realization of a telemetric IOP sensor for integration into an artificial intraocular lens. Such a device will open new perspectives, not only in the management of glaucoma, but also in basic research for mechanisms of glaucoma.

Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits.

BACKGROUND: In the ongoing discussion concerning the realization of an epiretinal prosthesis for electric stimulation of retinal ganglion cells, long-term fixation of such a device is a crucial question. We evaluated surgical techniques for implantation and fixation of electrically inactive microelectrode arrays (MA) into the retinas of rabbits and secondary tissue reactions to the implant. METHODS: Vitrectomy and laser coagulation of the prospective fixation area were performed in rabbits. Implantation of MAs was performed 3 weeks later in 10 animals. The MA was fixated using retinal tacks. The follow-up included ophthalmoscopy and electrophysiology. At the end of the follow-up, the enucleated eyes were processed for light microscopy using standard procedures and grinding techniques. RESULTS: Nine of 10 rabbits were implanted without serious complications. Clinical and electrophysiologic data through 6 months of follow-up did not indicate any adverse effect of the surgery, the implant, or the tack itself. No change in retinal architecture underneath the implant was found by light microscopy. In these cases, the implant was stable at its original fixation area. In three cases, mild cataract formation was observed, and in one case, a total retinal detachment was found. CONCLUSION: Tack fixation of electrode arrays for electric stimulation of the inner retinal surface seems to be a useful approach in long-term implantation of an epiretinal prosthesis.

Specific lysis of melanoma cells by receptor grafted T cells is enhanced by anti-idiotypic monoclonal antibodies directed to the scFv domain of the receptor.

Malignant transformation of melanocytes is frequently associated with abnormalities in antigen processing and in human leukocyte antigen class I antigen expression. Here, we evaluated a human leukocyte antigen class I antigen-independent approach to target cytotoxic T lymphocytes to melanoma cells by grafting cytotoxic T lymphocytes with a chimeric receptor that consists of both a domain binding to high molecular weight-melanoma associated antigen and a cellular activation domain. The binding domain is a single-chain antibody fragment (scFv) derived from the monoclonal anti-high molecular weight-melanoma associated antigen antibody 763.74 by phage display techniques. The cellular activation domain is the signaling unit of the FcepsilonRI receptor gamma chain. Both domains constitute the chimeric receptor scFv763.74-gammaR. Cytotoxic MD45 T cells grafted with the scFv763.74-gammaR receptor bind specifically to high molecular weight-melanoma associated antigen-positive melanoma cells and lyse melanoma cells in a human leukocyte antigen class I independent fashion. Pre-incubation of receptor grafted T cells with immobilized anti-idiotypic (id) monoclonal antibody MK2-23 binding to the scFv domain of the receptor enhanced the lysis of melanoma cells indicating that the specific cytolytic activity of receptor grafted T cells can be increased by costimulation with cross-linked anti-idiotypic monoclonal antibodies that recognize the antigen binding domain of the chimeric receptor.

The analysis of tyrosinase-specific mRNA in blood samples of melanoma patients by RT-PCR is not a useful test for metastatic tumor progression.

Reverse transcription (RT) of the tyrosinase mRNA and specific cDNA amplification by nested polymerase chain reactin (PCR) have been reported to facilitate the early detection of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. In the current study we analyzed peripheral blood samples of 65 melanoma patients of different clinical stages for the presence of tyrosinase mRNA by RT-PCR using nested oligonucleotide primers specific for tyrosinase cDNA. Furthermore, blood samples were evaluated for tumor cell growth by cell culture assays in vitro. No tyrosinase mRNA was detectable in blood samples of 26 patients with primary melanoma and 16 patients with regional lymph node metastases. In five of 13 patients with visceral metastases we found at least one blood sample positive for tyrosinase mRNA during a 2-to 4-mo interval. Analyses of different blood samples of patients with visceral metastases taken in a 2-h interval, furthermore, indicate that tumor cells only transiently persist in the peripheral blood. We obtained in vitro proliferating melanoma cells from two blood samples derived from different patients with visceral melanoma metastases. This demonstrates that viable melanoma cells indeed circulate in the peripheral blood with retained proliferative capacity in vitro. The analysis of blood samples by RT-PCR for tyrosinase mRNA, however, is not suitable for the early detection of tumor progression in melanoma patients.