While retinal degenerations encompass a wide range of molecular causes, the common final event is the death of photoreceptor cells and/or other retinal neurons resulting in irreversible blindness. Consequently, protecting photoreceptors from degeneration can be regarded as the key objective for future therapeutic strategies.
Our research focus is to identify and validate potential neuroprotective factors which are produced by the main glial cells of the retina: the Müller glial cells (Hauck and Ueffing, Arch Soc Esp Oftalmol. 2009). These cells contribute to intrinsic neuroprotection under the influence of disease-induced activation; however, they also transmit as yet unknown paracrine factors upon stimulation with e.g. glial cell line-derived neuroprotective factor (GDNF) (Hauck et al., MCB 2006). With a combined transcriptomics and proteomics approach, we currently dissect the GDNF-induced molecular events in primary retinal Müller cells and validate the neuroprotective potential of identified candidate factors by in vitro cellular assays (Hauck et al., MCP 2008) and in animal models of Retinitis Pigmentosa in situ as well as in vivo (DelRio et al., ongoing).
This work has been funded by a grant from the EU (6th framework, EVI-Genoret) and the Foundation Fighting Blindness and the translation of potential candidate factors into future therapies is further developed in the HOPE consortium (BMBF - HOPE). Since retinal Müller glial cells additionally to secretion of neuroprotective factors also harbour stem cell properties, another potential route into therapy could be the replacement of degenerationg photoreceptors by transdifferentiating Müller glial cells. Within the EU-funded Marie-Curie Training Network EduGlia we analyse retinal Müller glial cells in different developmental stages to gain further insights into these mechanisms.