Institute for Ophthalmic Research

Head

Prof. Dr. rer. nat. Marius Ueffing

Institute Director

Email: marius [dot] ueffing [at] uni-tuebingen [dot] de

Contact

Division of Experimental Ophthalmology
Centre for Ophthalmology
Institute for Ophthalmic Research
Röntgenweg 11
72076 Tübingen        

Mission statement

Inherited retinal degenerations such as Retinitis Pigmentosa (RP)are a major cause of blindness in industrialized countries. In the division of experimental ophthalmology we are seeking to develop treatments for RP and related diseases that affect photoreceptors. We argue that neuroprotection or cell replacement as a survival- and function-upholding regime is a feasible approach to preserve functional vision in patients affected by inherited retinal degenerations.

We use different animal models for RP as well as retinal explant cultures to study signalling pathways that are involved in photoreceptor cell death or survival. Insights into these mechanisms are crucial for the successful development of potential therapies. Based on these, different neuroprotective strategies are evaluated for their capacity to prevent or delay photoreceptor cell death. Another approach to preserve vision is the replacement of diseased cells by transplantation of retinal progenitors that are induced to differentiate into functional photoreceptors and integrate into the pre-existing retinal networks.

In the course of our research we have established that treatment with a combination of the neurotrophic factors CNTF and BDNF partially rescues photoreceptors. Furthermore, we have identified several factors important for photoreceptor degeneration including calpain-type proteases and poly-ADP-ribose-polymerase (PARP).

A retinal explant in culture

Based on our findings on cell death mechanisms, we believe that neuroprotective treatments combined with a replacement of diseased cells constitutes the most promising approach to preserve and restore functional vision.

Staining for degenerating cells (TUNEL) on wild-type (wt) and retinal degeneration (rd1) retinal cross-sections at postnatal day 11.

Cross-sections through a wild-type (wt) and retinal degeneration (rd1) retina at postnatal day 30.

Selected publications

Pinzon-Duarte, G., Arango-Gonzalez, B. Guenther, E. and Kohler, K. (2004) “Effects of brain-derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Muller glia cells in the developing retina.”, European Journal of Neuroscience 19:1475-1484.

Paquet-Durand, F., Azadi, S., Hauck, S. M., Ueffing, M., van Veen, T., Ekström, P. (2006): “Calpain is activated in degenerating photoreceptors in the rd1 mouse”, Journal of Neurochemistry 96: 802-814.

Azadi, S., Johnson, L., Paquet-Durand, F., Perez, M.-T., Zhang, Y., van Veen, T., Ekström P. (2007): “CNTF + BDNF treatment and neuroprotective pathways in the rd1 mouse retina.”, Brain Research 1129: 116-129.

Paquet-Durand, F., Silva, J., Talukdar, T., Johnson, L., Azadi, S., Hauck, S., Ueffing, M., van Veen, T., Ekström, P. (2007): “Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to inherited photoreceptor degeneration in the rd1 mouse.”, Journal of Neuroscience 27: 10311-10319.

Kustermann, S., Bolz, S., Hildebrandt, H. and Kohler, K. "Polysialylated NCAM in embryonic and adult neurogenesis in the zebrafish retina", to be published.