TU Dresden


Photoreceptor degeneration is a major cause of blindness, and at the CRTD, the retina has also become a focus for translating basic research toward clinical relevance.

In the zebrafish, the group of Prof. Michael Brand has developed novel conditional lesion models to analyze photoreceptor degeneration and regeneration in the adult retina. Photoreceptors that had been specifically ablated after conditional block of Fgf signaling regenerated from dividing progenitors and restored the layered structure of the retina with integration of new photoreceptor cells (Hochmann et al., 2012).

Proof-of-concept studies by Prof. Marius Ader's group established that transplantation of young photoreceptor cells into the adult mouse retina allows integration into the outer nuclear layer and formation of mature photoreceptors (Bartsch et al., 2008; Eberle et al., 2011, 2012). By injection of cone-like photoreceptors into the retina of a mouse model of cone photoreceptor degeneration the group provided the first evidence of functional repair of daylight responses by cell transplantation (Santos-Ferreira et al., 2015). Furthermore, they showed the unprecedented formation of extensive polarized cell monolayers following transplantation of human ESC-derived retinal pigment epithelium (RPE) into a mouse model of complete RPE loss (Carido et al., 2014). The Ader group aims to use mouse and human ESC- and iPSC-derived rod and cone photoreceptors in mouse models of complete blindness to evaluate their use as therapeutic agents for the treatment of retinal degeneration.

The group of Dr. Mike O. Karl has developed an ex vivo mouse retina regeneration assay, which they used to investigate mechanisms of Müller glia (MG) cell derived neuronal regeneration and revealed that MG derived neurogenesis is age-dependent (Löffler et al. 2015). The group will perform cell fate analysis of the Müller glia (MG) derived progeny in the damaged mouse retina model and explore ways to stimulate defined MG-derived neuronal cell types. The Karl lab received the Novartis' Research Project award in 2012 their project to develop new approaches for studying retinal gliosis and scar formation. The Karl group has also developed and optimized a protocol for pluripotent stem cells (PSC) derived retina organoidogenesis (Völkner et al. in review). They currently are developing a human retina disease model using human induced PSC-derived retina organoids from patients with CLN3 (Batten) disease, which results from a CLN3 mutation.  The project received the Eyenovative Novartis Research Award in 2014. Together with the groups of Prof. Ader and Prof. Tanaka, the use of human retinal pigment epithelium as a therapeutic agent and drug target for retinal diseases is being pursued (Carido et al., 2014; Zhu et al., 2013).

Dr. Volker Busskamp's group research interest strives to understand the functions of microRNAs in adult cone photoreceptors (Busskamp et al., 2014a) and demonstrated that two microRNA species were crucial for the maintenance of light-sensitive subcellular compartments of photoreceptors. A key interest lies in elucidating gene regulatory networks operating during neuronal differentiation from human iPSC (Busskamp et al., 2014b). The Busskamp group is also exploring transcription factor combinations to drive rapid neuronal differentiation to various neuronal cell types, and aims create functional synthetic human neuronal circuits in combination with optogenetic activation and electrophysiological recordings as biomedical testbeds. Disease specific mutations will be investigated using Cas9/CRISPR or by using iPSC derived from patients.

  • Bartsch U, Oriyakhel W, Kenna PF, Linke S, Richard G, Petrowitz B, Humphries P, Farrar GJ, and Ader M. (2008). Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice. Exp Eye Re 86:691-700.
  • Busskamp V, Krol J, Nelidova D, Daum J, Szikra T, Tsuda B, Juttner J, Farrow K, Scherf BG, Alvarez CP, et al. (2014a). miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function. Neuron 83:586-600.
  • Busskamp V, Lewis NE, Guye P, Ng AH, Shipman SL, Byrne SM, Sanjana NE, Murn J, Li Y, Li S, et al. (2014b). Rapid neurogenesis through transcriptional activation in human stem cells. Mol Sys Biol. 10:760.
  • Carido M, Zhu Y, Postel K, Benkner B, Cimalla P, Karl MO, Kurth T, Paquet-Durand F, Koch E, Munch TA, et al. (2014). Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation. Investig Ophthalmol Vis Science 55:5431-5444.
  • Eberle D, Schubert S, Postel K, Corbeil D, and Ader M. (2011). Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina. Investigative ophthalmology & visual science 52:6462-6471.
  • Eberle D, Kurth T, Santos-Ferreira T, Wilson J, Corbeil D, and Ader, M. (2012). Outer segment formation of transplanted photoreceptor precursor cells. PloS one 7:e46305.
  • Hochmann S, Kaslin J, Hans S, Weber A, Machate A, Geffarth M, Funk RH, and Brand M. (2012). Fgf signaling is required for photoreceptor maintenance in the adult zebrafish retina. PloS One 7:e30365.
  • Löffler K, Schäfer P, Völkner M, Holdt T & Karl MO. (2015). Age-dependent Müller glia stem cell competences in the mouse retina. Glia. 63:1809-24.
  • Santos-Ferreira T, Postel K, Stutzki H, Kurth T, Zeck G, and Ader M. (2015). Daylight vision repair by cell transplantation. Stem Cells 33:79-90.
  • Völkner MV, Zschätzsch, Rostovskaya M, Overall RW, Busskamp V, Anastassiadis K & Karl MO. (2016). Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. (in review)
  • Zhu Y, Carido M, Meinhardt A, Kurth T, Karl MO, Ader M, and Tanaka EM. (2013). Three-dimensional neuroepithelial culture from human embryonic stem cells and its use for quantitative conversion to retinal pigment epithelium. PloS One 8:e54552.