[Photoreceptor Transplantation into the Degenerative Retina]. / Photorezeptortransplantation in die degenerative Netzhaut.

Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models. This includes defining the necessary conditions, like the optimal ontogenetic stage of transplantable donor photoreceptors, cell-specific enrichment procedures and robust transplantation technologies. Moreover, first studies provided evidence for functional improvements by photoreceptor transplantation in mouse models of retinal dysfunction. Furthermore, advances in cell culture technology were made by introducing methods to generate photoreceptor-containing retinal organoids, derived from pluripotent stem cells, that provide theoretically unlimited sources for the production of photoreceptor transplants. Interestingly, the recently identified transfer of cytoplasmic material between donor and host photoreceptors might represent an additional treatment option for cell transplantation approaches. Within this review, we focus on the main developments within the photoreceptor transplantation field and discuss important achievements, challenges and hurdles to develop photoreceptor transplantation towards clinical applications.

Survivin silencing as a promising strategy to enhance the sensitivity of cancer cells to chemotherapeutic agents.

Since clinical application of conventional cancer therapies is usually limited by drug resistance and toxic side effects, combination of chemotherapeutic agents with gene therapy appears as an attractive therapeutic strategy to overcome these issues. Being selectively expressed in tumor tissues, survivin is a promising target for the development of anticancer strategies aimed at eliminating tumor cells while sparing normal tissues. In this work, we achieved substantial protein knockdown in a number of human cell lines, namely, A549, HeLa and MCF-7 cells which overexpress survivin, after treatment with anti-survivin siRNAs, which was associated with a significant reduction of cell viability, when compared to treatment with control siRNAs. Interestingly, when the survivin-silencing approach was combined with a chemotherapeutic agent, an enhancement of the therapeutic effect was achieved. Treatment with anti-survivin siRNAs resulted in high levels of caspase 3/7 activation, and an enhancement of this effect was observed when survivin silencing was combined with vinblastine. In addition, we showed that for A549 and HeLa cells survivin silencing contributes to the reversion of cell resistance to doxorubicin. Overall, we demonstrate that the combination of a survivin-directed silencing strategy with chemotherapeutic agents constitutes a valuable approach for cancer treatment.