Alpha2-adrenergic receptors and their core involvement in the process of axonal growth in retinal explants.

Authors:
Verena Prokosch
Verena Prokosch
School of Medicine
Germany
Lambros Panagis
Lambros Panagis
Departments of Cell Biology
Accra | Ghana
Gerd Fabian Volk
Gerd Fabian Volk
Jena University Hospital
Germany
Caterina Dermon
Caterina Dermon
Boston University
United States
Solon Thanos
Solon Thanos
School of Medicine
Germany

Invest Ophthalmol Vis Sci 2010 Dec 30;51(12):6688-99. Epub 2010 Jun 30.

Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Münster, Germany.

Purpose: To determine the patterns of α2-adrenergic receptor (α2-AR) subtype expression in normal and degenerated retinas and to analyze the response of these receptors to the α2-AR agonist brimonidine tartrate (BT).

Methods: The binding characteristics of α2-ARs in the retina were evaluated in experimental and matching sham groups by in vitro quantitative autoradiographic saturation with [(3)H]-clonidine. Retinal explants from juvenile and adult rats with either elevated intraocular pressure or after optic nerve crush (ONC) were cultured with BT over 96 hours in vitro to analyze the effects of BT on axonal growth by videomicroscopy and axon counting. Changes in retinal protein expression by BT were monitored by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS).

Results: The total number of α2-ARs in the retina increased significantly after ONC compared with the sham group. BT supported axonal growth in the juvenile, glaucomatous, and injured retinas (P < 0.004) most effectively at a concentration of 0.001 mg/mL, without influencing the axonal growth rate. Immediate supplementation of BT was more effective than delayed supplementation (P < 0.001). Proteomic analysis revealed treatment-specific expression patterns of glial fibrillary acidic protein (GFAP), glucose-related protein (GRP)58, platelet-activating factor (PAF), and laminin-binding protein (LBP).

Conclusions: These data are the first to show differences in α2-AR expression in normal and degenerated retinas. BT supports neuronal growth in cultured retinal pieces, suggesting that α2-ARs play a role in retinal metabolism.

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http://dx.doi.org/10.1167/iovs.09-4835DOI Listing

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December 2010
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