Biochemical and biomechanical modulation of the in vitro retina

Abstract: The porcine retinal explant culture paradigm offers the possibility to study retinal health, disease and development independently from the surrounding tissues of the eye. Retina-intrinsic effects of molecular and mechanical cues on the isolated retinal sheet can thus be studied with great precision. For the purpose of creating a donor tissue optimized for transplantation, we used this system to explore the impact of biochemical modulation on cell survival and embryogenesis. Further, biomechanical modulation and its significance in retinal homeostasis was investigated. Biochemical modulation of the embryonic retina using glutamate revealed an accelerated photoreceptor maturation coupled with increased developmental apoptosis in the inner layers. In adult tissue, glial cell-derived neurotrophic factor (GDNF) treatment was found to increase photoreceptor cell survival and attenuate gliosis. These results demonstrate the potential of biochemical modulation in the creation of a donor tissue well adapted for retinal transplantation. Biomechanical modulation through emulation of the tissue tension and inner retinal support found in the living eye was found to significantly increase neuronal survival and preserve glial structure and function in adult explants. The results demonstrate the importance of the biomechanical milieu for retinal homeostasis and provide an important link between glial cell health and neuronal preservation. In conclusion, we have shown that biochemical and biomechanical modulation of the porcine retina in vitro can be used to modify development and enhance cell survival. The findings provide further understanding of mechanisms behind retinal disease and reveals new avenues in the search for treatment of degenerative retinal disease.