Previous and current research

Loss of sight as a result of dysfunction/degeneration of retinal cells is a major cause of disability. Eye diseases caused by degeneration of photoreceptors include e.g. retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, or cone-rod dystrophy. The immense genetic heterogeneity that causes photoreceptor degeneration (e.g. for retinitis pigmentosa alone mutations in more than 40 genes with up to 150 different mutations in a single gene are known) makes it difficult to develop therapeutical interventions for these diseases.

One possible strategy to treat loss of photoreceptors involves cell-based approaches, which might be of more general use since in principle many different pathogenic mutations might be treatable by the same source of cells. Recently it has been demonstrated that precursors committed to the photoreceptor fate rather than stem cells have the potential to integrate into host retinas and differentiate into mature photoreceptors following transplantation into adult mice. Primary cells directly isolated from the developing retina were used in these experiments. Although primary retinal cells provide an excellent tool to test cell-therapeutic approaches for retinopathies, the use of these cells as a cell source for therapies in humans might be difficult due to significant problems associated with availability and logistics beside ethical concerns. Thus, an expandable cell source, like stem cells, that can be pre-differentiated in vitro into photoreceptor precursors might be ideal for the development of cell-based therapies for retinopathies.

We use cells isolated from the developing retina or pluripotent stem cells and stimulate their differentiation into photoreceptors. The detailed characterization of primary retinal cells that have the potential to correctly integrate and differentiate into mature photoreceptors will enable the selection of the optimal cell-type from expandable stem cell sources for transplantation. Transplantation experiments into mouse models that are characterized by photoreceptor degeneration will be performed to test the potential of cell replacement strategies to restore visual function.

5 Future projects and goals

1. stimulation of expandable stem/progenitor cells for the generation of photoreceptors
2. characterisation of the best integrating and photoreceptor forming cell-type
3. manipulation of host tissue to enhance cell integration
4. transplantation of cells into mouse models of retinopathies
5. analysis of integrated cells: morphology, expression patterns, synaptic connections, functionality

Integration of cells isolated from the neonatal retina of rhodopsin-EGFP/actin-DsRed double reporter mice three weeks after subretinal transplantation into an adult mouse. Donor cells ubiquitously expressing DsRed (red) integrated into the outer nuclear layer (ONL) and generated mature photoreceptors containing an outer segment identified by a rhodopsin-EGFP fusion construct (green). INL: inner nuclear layer; IPL: inner plexiform layer; IS: inner segments; ONL: outer nuclear layer; OPL: outer plexiform layer; OS: outer segments.

For further information please visit our film "Hilfe für das Auge"

Vision Research in Dresden

Group Members

List of group members

Selected Publications

Eberle D, Schubert S, Postel K, Corbeil D, Ader M (2011) Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina. IOVS, in press.

Roehlecke C, Schumann S, Ader M, Knels L, Funk RHW (2011) Influence of blue light on photoreceptors in a live retinal explant system. Mol Vis, 17:876-884.

Mansergh FC, Vawda R, Millington-Ward S, Kenna PF, Wilson JH, Humphries P, Ader M, Farrar GJ (2010) Loss of photoreceptor potential from retinal progenitor cell cultures, despite improvements in survival. Exp Eye Res, 91(4):500-12.

Tanner G, Glaus E, Ader M, Barthelmes D, Fleischauer J, Pagani F, Berger W, Neidhardt J (2009) Therapeutic strategy to rescue mutation-induced exon skipping in rhodopsin by adaptation of U1 snRNA. Hum Mut, 30(2):255-63.

Bartsch U, Oriyakhel W, Kenna PF, Linke S, Richard G, Petrowitz B, Humphries P, Farrar GF, Ader M. (2008) Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into the adult mouse. Exp Eye Res, 86(4):691-700.

Tam LC, Kiang AS, Kennan A, Kenna PF, Chadderton N, Ader M, Palfi A, Aherne A, Campbell M, Reynolds A, McKee A, Humphries MM, Farrar J, Humphries P (2008) Therapeutic benefit derived from RNAi-mediated ablation of IMPDH1 transcripts in a murine model of autosomal dominant retinitis pigmentosa (RP10). Hum Mol Genet 17:2084-2100

O'Reilly M, Palfi A, Chadderton N, Millington-Ward S, Ader M, Cronin T, Tuohy T, Auricchio A, Hildinger M, Tivnan A, McNally N, Humphries MM, Kiang AS, Humphries P, Kenna PF, Farrar GJ. (2007) RNA interference-mediated suppression and replacement of human rhodopsin in vivo. Am J Hum Genet 81(1):127-35.

Palfi A, Ader M, Kiang AS, Millington-Ward S, Clark G, O’Reilly M, McMahon HP, Kenna PF, Humphries P, Farrar GJ (2006) RNAi-based suppression and replacement of rds/peripherin in retinal organotypic cuture. Hum Mut 27(3):260-8