[Current therapeutic approaches in inherited retinal degeneration: from genes to chip]. / Therapieansätze für erbliche Netzhauterkrankungen: von den Genen bis zum Chip.

Different strategies for the treatment of inherited photoreceptor degeneration are currently being investigated, with each of these approaches facing specific challenges. Gene therapy, for instance, may be feasible only for genetically well-defined pathologies. However, inherited retinal disorders are genetically highly heterogeneous and early onset disorders may restrict the therapeutic window. The majority of currently developed molecular approaches aim at the reconstitution of physiologically important functions in RPE and photoreceptor. Neuroprotection attempts to prolong cell survival and proper function via sustained delivery systems that fulfil a long-term dynamic reservoir function for therapeutic neuroprotective compounds. Cell-based approaches include replacement strategies such as cell transplantation, the implantation of prosthetic devices or optogenetics. They aim at replacing lost neurosensory functions of the retina. This short review aims at providing an insight into current therapeutic strategies and future treatment options for retinal disorders. Pharmacological and nutritional support strategies are only briefly discussed as we focus here on molecular and prosthetic therapeutic approaches.

Neurons and glia in the midline of the higher crustacean Orchestia cavimana are generated via an invariant cell lineage that comprises a median neuroblast and glial progenitors.

Midline cells are a common feature of both insects and crustaceans. Midline cells in the insects Schistocerca americana and Drosophila melanogaster have been shown to give rise to pairs of either neurons or glial cells (midline precursor) as well as to repeatedly generate neurons (median neuroblast) or both neurons and glia (median neuroglioblast). This study addresses midline cell lineages in a higher crustacean, the amphipod Orchestia cavimana. In vivo labeling of single midline cells shows that the resulting cell lineage is invariant and that these cells act as progenitors for sets of three glial precursors and one median neuroblast. The progeny are restricted to parasegmental units. The glial precursors give rise to three pairs of glial cells; two of them enwrap the commissures. The median neuroblast gives rise to about 10 cells that differentiate into 3 classes of neurons. The presence of median neuroblasts is also shown for another higher crustacean, the isopod Porcellio scaber using BrdU labeling. This is the first study to analyze the cell lineage of crustacean neurons generated by early ectodermal precursors. A comparison with those of insects demonstrates both conservation and change during the evolution of arthropods.

Cell lineage of the midline cells in the amphipod crustacean Orchestia cavimana (Crustacea, Malacostraca) during formation and separation of the germ band.

Cell lineages of identified midline cells were traced in the amphipod Orchestia cavimana (Crustacea, Malacostraca) by in vivo labelling. Midline cells are a common phenomenon in the germ band of crustaceans and insects. Studies in midline cells of Drosophila showed an origin from separate, paired anlagen and a differentiation into three types of cells. The in vivo labelling of midline cells of Orchestia demonstrates that they originate from the same material as the neural and epidermal ectoderm, divide in a stereotyped cell division pattern and give rise to at least two different types of cells. During the following evolutionarily derived mode of germ band elongation in Orchestia, a morphogenetic process is intercalated that separates germ band halves. On the level of single cells, it can be shown that midline cells are the only ectodermal cells that bridge the large distance between the separated parts. The cells are stretched extensively but do not proliferate. Comparing the midline cells of Orchestia with non-malacostracan crustaceans and insects, the results favour the hypothesis that midline cells are a distinct population of cells homologous in crustaceans and insects.

The pattern of Distal-less expression in the mouthparts of crustaceans, myriapods and insects: new evidence for a gnathobasic mandible and the common origin of Mandibulata.

We examined embryos of representatives of crustaceans, myriapods and insects with respect to DII expression in the mouthparts. In order to examine the relationships between mandibular DII expression and the occurrence of a mandibular palp we compared amphipod, isopod and decapod crustacean species. In species with mandibular palps, DII expression is maintained throughout development and is restricted to the palps. The species lacking a palp as an adult show only transient DII expression in early embryonic stages. Furthermore, we studied mandibular DII expression in the myriapod Glomeris marginata that lacks like all myriapods mandibular palps as an adult. The expression pattern is similar to that in crustaceans lacking a palp as an adult. We examined entognathous and ectognathous insects. No sign of mandibular expression could be detected. It is shown that the distal parts of the mandibular appendage were reduced in several steps and lineages independently up to a total loss. Furthermore, we studied DII expression in the first and second maxillae. Except for Glomeris and the collembolans, the first maxillae of all species show a similar pattern of three lobes expressing DII: the outer expression marks the maxillary palp and the inner two mark the outgrowing endites (galea and lacinia of insects). In the first maxillae of collembolans only two expression areas could be detected. In palpless adult first maxillae of isopod crustaceans a transitory embryonic palp occurs which is also DII positive. In the second maxillae of insects, isopod and amphipod crustaceans only two DII-positive lobes occur. Our data suggest a gnathobasic character of the mandibles of crustaceans, myriapods and insects supporting the monophyly of Mandibulata sensu Snodgrass. The interpretation of DII expression patterns and its limits are critically evaluated.