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Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells.

ABSTRACT: PURPOSE. To describe how developing amacrine cells and retinal ganglion cells (RGCs) differ in survival signaling and global gene expression. METHODS. Amacrine cells were immunopurified and processed for gene microarray analysis. For survival studies, purified amacrine cells were cultured at low density in serum-free medium, with and without peptide trophic factors and survival pathway inhibitors. The differences in gene expression between amacrine cells and RGCs were analyzed by comparing the transcriptomes of these two cell types at the same developmental ages. RESULTS. The amacrine cell transcriptome was very dynamic during development. Amacrine cell gene expression was remarkably similar to that of RGCs, but differed in several gene ontologies, including polarity- and neurotransmission-associated genes. Unlike RGCs, amacrine cell survival in vitro was independent of cell density and the presence of exogenous trophic factors, but necessitated Erk activation via MEK1/2 and AKT signaling. Finally, comparison of the gene expression profile of amacrine cells and RGCs provided a list of polarity-associated candidate genes that may explain the inability of amacrine cells to differentiate axons and dendrites as RGCs do. CONCLUSIONS. Comparison of the gene expression profile between amacrine cells and RGCs may improve our understanding of why amacrine cells fail to differentiate axons and dendrites during retinal development and of what makes amacrine cells differ in their resistance to neurodegeneration. Switching RGCs to an amacrine cell-like state could help preserve their survival in neurodegenerative diseases like glaucoma, and amacrine cells could provide a ready source of replacement RGCs in such optic neuropathies.

SUBMITTER: Kunzevitzky NJ

PROVIDER: S-EPMC2904021 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells.

Kunzevitzky Noelia J NJ Almeida Monica V MV Goldberg Jeffrey L JL

Investigative ophthalmology & visual science 20100505 7

PURPOSE. To describe how developing amacrine cells and retinal ganglion cells (RGCs) differ in survival signaling and global gene expression. METHODS. Amacrine cells were immunopurified and processed for gene microarray analysis. For survival studies, purified amacrine cells were cultured at low density in serum-free medium, with and without peptide trophic factors and survival pathway inhibitors. The differences in gene expression between amacrine cells and RGCs were analyzed by comparing the t ...[more]

PMID: 20445109

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Project description:All superclasses of retinal neurons, including bipolar cells (BCs), amacrine cells (ACs) and ganglion cells (GCs), display gap junctional coupling. However, coupling varies extensively by class. Heterocellular AC coupling is common in many mammalian GC classes. Yet, the topology and functions of coupling networks remains largely undefined. GCs are the least frequent superclass in the inner plexiform layer and the gap junctions mediating GC-to-AC coupling (GC::AC) are sparsely arrayed amidst large cohorts of homocellular AC::AC, BC::BC, GC::GC and heterocellular AC::BC gap junctions. Here, we report quantitative coupling for identified GCs in retinal connectome 1 (RC1), a high resolution (2 nm) transmission electron microscopy-based volume of rabbit retina. These reveal that most GC gap junctions in RC1 are suboptical. GC classes lack direct cross-class homocellular coupling with other GCs, despite opportunities via direct membrane contact, while OFF alpha GCs and transient ON directionally selective (DS) GCs are strongly coupled to distinct AC cohorts. Integrated small molecule immunocytochemistry identifies these as GABAergic ACs (?+ ACs). Multi-hop synaptic queries of RC1 connectome further profile these coupled ?+ ACs. Notably, OFF alpha GCs couple to OFF ?+ ACs and transient ON DS GCs couple to ON ?+ ACs, including a large interstitial amacrine cell, revealing matched ON/OFF photic drive polarities within coupled networks. Furthermore, BC input to these ?+ ACs is tightly matched to the GCs with which they couple. Evaluation of the coupled versus inhibitory targets of the ?+ ACs reveals that in both ON and OFF coupled GC networks these ACs are presynaptic to GC classes that are different than the classes with which they couple. These heterocellular coupling patterns provide a potential mechanism for an excited GC to indirectly inhibit nearby GCs of different classes. Similarly, coupled ?+ ACs engaged in feedback networks can leverage the additional gain of BC synapses in shaping the signaling of downstream targets based on their own selective coupling with GCs. A consequence of coupling is intercellular fluxes of small molecules. GC::AC coupling involves primarily ?+ cells, likely resulting in GABA diffusion into GCs. Surveying GABA signatures in the GC layer across diverse species suggests the majority of vertebrate retinas engage in GC::?+ AC coupling.

Dataset Information

Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells.

Publications

Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells.

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