Human ganglion cells express the alpha-2 adrenergic receptor: relevance to neuroprotection - PubMed (original) (raw)

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Human ganglion cells express the alpha-2 adrenergic receptor: relevance to neuroprotection

F B Kalapesi et al. Br J Ophthalmol. 2005 Jun.

Abstract

Background/aim: Alpha-2alpha adrenergic receptor (alpha(2)-AR) agonists are thought to be neuroprotective, preventing retinal ganglion cell death independent of pressure reduction. Previous studies have identified alpha(2)-ARs in rat retina. The authors aimed to demonstrate the presence and localisation of alpha(2)-ARs in human and rat retina and on the rat retinal ganglion cell line, RGC-5.

Methods: Seven postmortem human and three postmortem rat eyes were paraformaldehyde fixed and frozen. RGC-5 cells were also paraformaldehyde fixed. The expression of alpha(2A)-ARs was determined by antibody immunofluorescence.

Results: alpha(2A)-AR expression was identified in the human retina, on ganglion cells, and cells in the inner and outer nuclear layers (INL, ONL). Differential alpha(2A)-AR staining patterns in the INL and ONL suggest a further restriction to as yet unidentified neuronal subclasses. The RGC-5 cell line also expressed alpha(2A)-ARs in undifferentiated cells and an increased expression upon fully differentiated cells.

Conclusion: alpha(2)-AR agonists in addition to their pressure lowering effects in the eye, may act directly upon retinal neurons, including retinal ganglion cells. The presence of alpha(2)-ARs on the RGC-5 cell line allows future investigation of these possible direct effects using in vitro glaucoma model systems.

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Figures

Figure 1

Figure 1

α2A-AR expression in the rat retina. Confocal images of rat retina labelled with α2A-AR antibody throughout retinal layers. (A) Shows positive immunostaining for the α2A-AR on retinal ganglion cells, cells in the inner nuclear layer (INL) and less so, but also on the membrane of outer nuclear layer (ONL) cells. (C) A retina control with secondary antibody alone showing no non-specific staining. (B) and (D) are equivalent to (A) and (C) retinal sections, respectively, showing Hoechst nuclear counterstaining. All images are taken with the ×63 objective, (C) shows 25 μm scale bar. GCL, ganglion cell layer.

Figure 2

Figure 2

α2A-AR expression in the human cornea and retina. Confocal images of human eye labelled with α2A-AR antibody in cornea and retinal layers. (A), (E), and (G) Immunostained with α2A-AR antibody and (C) with chicken IgY alone. (B), (F), (H), and (D) Corresponding Hoechst nuclear counterstaining. (A) The positive control, is human corneal epithelium showing specific strong staining for the 2AR. (C) A retina control with chicken IgY alone showing no non-specific staining. (E) and (G) Staining of two different human retinas with positive retinal ganglion cells (arrows) and variable staining in inner (INL) and outer nuclear layers (ONL). Between different retinas, there was some variability in overall intensity but a similar pattern of staining. All images are taken with the ×63 objective. (G) Shows 25 μm scale bar. GCL, ganglion cell layer.

Figure 3

Figure 3

α2A-AR expression in the rat retinal ganglion cell line, RGC-5. Confocal images of rat retinal ganglion cell line RGC-5 labelled with α2A-AR antibody. (A) Undifferentiated RGC-5 cells have low, though positive, level of α2A-AR expression. (B-D) 3, 5, and 7 days, respectively, of RGC-5 differentiation, showing positive α2A-AR expression, with maximum expression at 7 days of differentiation. (E) (inset) RGC-5 cells with chicken IgY alone showing no non-specific staining. Identical staining and confocal imaging conditions used for all images. All images ×40 objective. (C) Shows 25 μm scale bar.

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