Marius Ader

Marius Ader
Technische Universität Dresden | TUD · Center for Regenerative Therapies Dresden

PhD

About

112
Publications
13,710
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Introduction
Marius Ader currently works at the Center for Regenerative Therapies Dresden , Technische Universität Dresden. Marius does research in Cell Biology and Vision Science.. Their current project is 'Transplantation of photoreceptor precursor cells into the adult mouse retina'.
Additional affiliations
October 2007 - present
Technische Universität Dresden
Position
  • Center for Regenerative Therapies, Dresden
August 2003 - February 2008
Trinity College Dublin
January 2003 - May 2003
University of Hamburg

Publications

Publications (112)
Article
Zusammenfassung Hintergrund Die Deutsche Ophthalmologische Gesellschaft (DOG) erfasst regelmäßig die wissenschaftlichen Aktivitäten der augenheilkundlichen Forschungseinrichtungen in Deutschland. Ziel der Arbeit Mit dieser Publikation will die DOG die Leistungsfähigkeit der wissenschaftlichen Augenheilkunde in Deutschland transparent machen und d...
Article
Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructure...
Article
Photoreceptor cell transplantation into the mouse retina has been shown to result in the transfer of cytoplasmic material between donor and host photoreceptors. Recently it has been found that this inter-photoreceptor material transfer process is likely to be mediated by nanotube-like structures connecting donor and host photoreceptors. By leveragi...
Article
Full-text available
Biomedical research relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells’ properties and should be avoided, especially when purifying cells for clinical applications. A promising alternativ...
Article
Full-text available
Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to dete...
Preprint
Full-text available
Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructure...
Preprint
Full-text available
Biomedical research often relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells' properties and should be avoided, especially when purifying cells for clinical applications. A promising alte...
Article
Full-text available
Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Our data show that up...
Article
Full-text available
Phagocytosis is a key function in various cells throughout the body. A deficiency in photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) causes vision loss in inherited retinal diseases and possibly age-related macular degeneration. To date, there are no effective therapies available aiming at recovering the lost...
Preprint
Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Up to 1.5% of precurso...
Article
Full-text available
Age-related macular degeneration (AMD) is a leading cause for visual impairment in aging populations with limited established therapeutic interventions available. Oxidative stress plays an essential role in the pathogenesis of AMD, damaging the retinal pigment epithelium (RPE), which is essential for the function and maintenance of the light-sensin...
Article
Full-text available
Potent neuroprotective effects of photobiomodulation with 670 nm red light (RL) have been demonstrated in several models of retinal disease. RL improves mitochondrial metabolism, reduces retinal inflammation and oxidative cell stress, showing its ability to enhance visual function. However, the current knowledge is limited to the main hypothesis th...
Article
Full-text available
Maintenance of a healthy photoreceptor-retinal pigment epithelium (RPE) interface is essential for vision. At the center of this interface, apical membrane protrusions stemming from the RPE ensheath photoreceptor outer segments (POS), and are possibly involved in the recycling of POS through phagocytosis. The molecules that regulate POS ensheathmen...
Article
Full-text available
Rod photoreceptors of nocturnal mammals display a striking inversion of nuclear architecture, which has been proposed as an evolutionary adaptation to dark environments. However, the nature of visual benefits and the underlying mechanisms remains unclear. It is widely assumed that improvements in nocturnal vision would depend on maximization of pho...
Chapter
Developing successful surgical strategies to deliver cell therapeutics to the back of the eye is an essential pillar to success for stem cell-based applications in blinding retinal diseases. Within this chapter, we have attempted to gather all key considerations during preclinical animal trials.Guidance is provided for choices on animal models, opt...
Article
Full-text available
A major challenge in the treatment of retinal degenerative diseases, with the transplantation of replacement photoreceptors, is the difficulty in inducing the grafted cells to grow and maintain light sensitive outer segments in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). Here, for an RP...
Article
Full-text available
Retinal hypoxia triggers abnormal vessel growth and microvascular hyper‐permeability in ischemic retinopathies. Whereas vascular endothelial growth factor A (VEGF‐A) inhibitors significantly hinder disease progression, their benefits to retinal neurons remain poorly understood. Similar to humans, oxygen‐induced retinopathy (OIR) mice exhibit severe...
Preprint
Full-text available
Rod photoreceptors of nocturnal mammals display a striking inversion of nuclear architecture, which has been proposed as an evolutionary adaptation to dark environments. However, the nature of visual benefits and underlying mechanisms remains unclear. It is widely assumed that improvements in nocturnal vision would depend on maximization of photon...
Article
Full-text available
Distinct cell‐types within the retina are mainly specified by morphological and molecular parameters, however, physical properties are increasingly recognized as a valuable tool to characterize and distinguish cells in diverse tissues. High‐throughput analysis of morpho‐rheological features has recently been introduced using real‐time deformability...
Data
Figure S2: CRX‐GFP + cells within cluster 1 and 2 show a similar expression of rod precursor marker NRL. A) Expression of NRL in cluster 1 and 2 shown through a violin plot profile; B) Immunostaining of retinal organoids at day 90 showing few GFP+ cells co‐stained with NRL (white arrows); B′) Inset: high magnification of NRL+ and CRX‐GFP+ cell. Sca...
Data
Figure S1: Stepwise filtering strategy of single cell RNA‐Seq data. A and B) Cells which had fewer than 150,000 reads or 2,000 genes were removed from downstream analysis; C) Cells with housekeeping genes of less than 20,000 counts were removed from analysis; D) Cells with higher than 10% mitochondrial genes were removed from analysis; E) Cells wit...
Data
Figure S3: CRX‐GFP + cells within cluster 1 show a cone biased transcriptional profile. A) Expression of ONECUT1, OLIG2 and OTX2 cone markers in cluster 1 and 2 shown through violin plot profiles; B) Immunostaining of retinal organoids at day 90 showing co‐staining of CRX‐GFP+ cells with OTX2; very few CRX‐GFP+ cells co‐localize with ONECUT1 (white...
Data
Table S1: Summary of antibodies used for immunohistochemical staining.
Data
Figure S4: Characterization of Pde6brd1 Mouse Model of Retinal Degeneration compared with Wild Type Mouse Retina. IHC imaged showing the different localization of retinal markers in Pde6brd1 Mouse Model of Retinal Degeneration and C57 Wild Type Mouse (WT). A‐B) Localization of pan‐photoreceptor marker (Recoverin) in WT retina in the OS/IS and ONL (...
Data
Table S2: List of significantly and differentially expressed genes between clusters 1 and 2.
Article
Full-text available
Death of photoreceptors is a common cause of age-related and inherited retinal dystrophies, thus their replenishment from renewable stem cell sources is a highly desirable therapeutic goal. Human pluripotent stem cells provide a useful cell source in view of their limitless self-renewal capacity and potential to differentiate not only into cells of...
Article
The mammalian retina displays no intrinsic regenerative capacities, therefore retinal degenerative diseases such as age-related macular degeneration (AMD) or retinitis pigmentosa (RP) result in a permanent loss of the light-sensing photoreceptor cells. The degeneration of photoreceptors leads to vision impairment and, in later stages, complete blin...
Preprint
Full-text available
A major challenge in the treatment of retinal degenerative diseases, with the transplantation of replacement photoreceptors, is the difficulty in inducing the grafted cells to grow and maintain light sensitive outer segments in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). For a RPE-indep...
Article
A major cause for vision impairment and blindness in industrialized countries is the loss of the light-sensing retinal tissue in the eye. Photoreceptor damage is one of the main characteristics found in retinal degeneration diseases, such as Retinitis Pigmentosa or age-related macular degeneration. The lack of effective therapies to stop photorecep...
Article
Full-text available
In this paper, we present a reliable and robust method for magnetomotive optical coherence tomography (MM-OCT) imaging of single cells labeled with iron oxide particles. This method employs modulated longitudinal and transverse magnetic fields to evoke alignment and rotation of anisotropic magnetic structures in the sample volume. Experimental evid...
Article
Full-text available
Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed...
Article
Full-text available
Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients. This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level, though the act...
Article
Full-text available
Vision represents one of the main senses for humans to interact with their environment. Our sight relies on the presence of fully functional light sensitive cells – rod and cone photoreceptors — allowing us to see under dim (rods) and bright (cones) light conditions. Photoreceptor degeneration is one of the major causes for vision impairment in ind...
Article
Pre-clinical studies provided evidence for successful photoreceptor cell replacement therapy. Migration and integration of donor photoreceptors into the retina has been proposed as the underlying mechanism for restored visual function. Here we reveal that donor photoreceptors do not structurally integrate into the retinal tissue but instead reside...
Article
Full-text available
Purpose: Preclinical studies on photoreceptor transplantation provided evidence for restoration of visual function with pluripotent stem cells considered as a potential source for sufficient amounts of donor material. Adequate preclinical models representing retinal disease conditions of potential future patients are needed for translation researc...
Article
Exposure to short wavelength light causes increased reactive oxygen intermediates production in the outer retina, particularly in the rod Outer Segments (OS). Consistently, the OS were shown to conduct aerobic ATP production through the ectopic expression of the electron transfer chain complexes I-IV and F1Fo-ATP synthase. These facts prompted us t...
Article
Full-text available
Point mutations in peripherin-2 (PRPH2) are associated with severe retinal degenerative disorders affecting rod and/or cone photoreceptors. Various disease-causing mutations have been identified, but the exact contribution of a given mutation to the clinical phenotype remains unclear. Exonic point mutations are usually assumed to alter single amino...
Data
Exon 2 specific disease associated point mutations in PRPH2. Left, the region of PRPH2 encoded by exon 2 is shown as a dashed rectangle. Right, schematic magnification of the exon 2-encoded part. Currently known positions of point mutations are highlighted in green. Arrowheads point to the mutations affecting the amino acids analyzed in this study....
Data
Determination of the linear amplification range of RT-PCR for PRPH2 minigenes. Representative qRT-PCR from retinas injected with WT PRPH2 minigenes harboring a rod hRHO (rP-mg) or cone mSWS (cP-mg) specific promoter. For qRT-PCR, the same pooled retina samples and the same primers were used as described in Fig 2B. The dashed lines represent the win...
Data
Representative sequence analyses of PRPH2 splice products. (A) Sequencing results of the exon boundaries from the correctly spliced PRPH2 transcript. Bottom left, topology of the correctly spliced PRPH2. The region encoded by exon 2 is given as a dashed rectangle. N, N-terminus, C, C-terminus. (B) Sequencing results of the G249S mutant. Upper panel...
Data
Representative fundus photography of murine retinas injected with single PRPH2 minigenes. Fundus photography images were performed three weeks post injection on wild type mice injected at the age of two weeks with the single PRPH2 minigenes under the control of a cone specific mSWS (A) or rod specific hRHO (B) promoter. Scale bar represents 800 μm....
Data
Sum of absolute band intensities for PRPH2 minigenes in rods and cones. The data shows the total sum of absolute intensities of all bands detected for each PRPH2 minigene from five technical replicates shown in RT-PCR experiments in Fig 2A. The bars represent the mean values ± SEM conducted to calculate the relative percentages displayed in Fig 2C–...
Data
In silico splice analysis of 30 point mutations in exon 2 of PRPH2. For splice analysis using ASSEDA prediction software, 40 bp flanking the respective mutation were used. All changes for single splice elements or donor and acceptor sites are shown as fold changes to the WT. For NNSplice based prediction, single scores are given for the WT PRPH2 an...
Data
Cross-expression of one rod-dominant PRPH2 mutant in cones and one cone-dominant mutant in rods. Protein localization (A, F), mRNA splicing (B, C, G, H), and protein expression (D, E, I, J) of a cone dominant R220W mutation in rods (A-E) and a rod-dominant W246R mutation in cones (F-J). The experimental conditions (age of injected mice, immunolabel...
Article
Cell transplantation and stem cell therapy are promising approaches for regenerative medicine and are of interest to researchers and clinicians worldwide. However, currently, no imaging technique that allows three-dimensional in vivo inspection of therapeutically administered cells in host tissues is available. Therefore, we investigate magnetomoti...
Article
Human daylight vision depends on cone photoreceptors and their degeneration results in visual impairment and blindness as observed in several eye diseases including age-related macular degeneration, cone-rod dystrophies, or late stage retinitis pigmentosa, with no cure available. Pre-clinical cell replacement approaches in mouse retina have been fo...
Article
Recently human embryonic stem cell research has taken on a new dimension — the third dimension. Capitalizing on increasing knowledge on directing pluripotent cells along different lineages, combined with ECM supported three-dimensional culture conditions, it has become possible to generate highly organized tissues of the central nervous system, gut...
Article
Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we descri...
Article
Full-text available
Loss of the light-sensing photoreceptors results in vision impairment and blindness, representing one of the main causes for disability in industrialized societies. Although the pathophysiology of diseases such as age-related macular degeneration, retinitis pigmentosa, or cone-rod dystrophies is highly heterogeneous, the final endpoint of such cond...
Chapter
Full-text available
Regenerative medicine includes several therapeutic strategies to replace degenerated tissue and/or cells or to restore physiological functions. Although a number of challenges must still be addressed, the potential of stem cells (SC) and/or progenitor cell-based regenerative medicine to treat a variety of chronic, traumatic or degenerative diseases...
Article
Vision impairment and blindness due to the loss of the light-sensing cells of the retina, i.e. photoreceptors, represents the main reason for disability in industrialized countries. Replacement of degenerated photoreceptors by cell transplantation represents a possible treatment option in future clinical applications. Indeed, recent preclinical stu...
Article
Full-text available
Purpose: In most mammalian species, retinal ganglion cell (RGC) axons are myelinated in the optic nerve, but remain nonmyelinated in the retinal nerve fiber layer and the most proximal (i.e., retina-near) region of the nerve. Here we analyzed whether RGCs are involved in the control of this characteristic distribution of oligodendrocytes and myeli...