RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina.

Abstract

BACKGROUND:

The death and the failure of neurons to regenerate their axons after lesion of the central nervous system in mammals, as in the case of spinal cord injury and optic nerve trauma, remain a challenge. In this study, we focused on the repulsive guidance molecule A (RGMA) and its receptor neogenin. Since it was reported that RGMA+ cells accumulate in lesioned areas after spinal cord injury, brain trauma, and optic nerve crush, and curiously, anti-apoptotic effects of RGMA were also described, we investigated the role of RGMA and neogenin in the retina after optic nerve crush (ONC).

METHODS:

We evaluated the spatial and temporal protein pattern of RGMA and neogenin in the rat retina without (non-regenerating model) or with (regenerating model) lens injury (LI). We investigated the presence of RGMA, neogenin and other proteins at up to nine time points (6 h-20 days post-surgery) by performing immunohistochemistry and Western blots.

RESULTS:

Independent of the treatment, RGMA protein was present in the nuclear layers (NLs), plexiform layers (PLs), nerve fiber layer (NFL), and in retinal ganglion cells (RGCs) of the rat retina. RGC and nerve fibers were always RGMA+. Further RGMA+ cells in the retina were blood vessel endothelial cells, astrocytes, Müller cells, and some microglial cells. The RGMA pattern for the specific retinal cells resembled those of previously published data. The neogenin pattern was congruent to the RGMA pattern. Western blots of retinal tissue showed further RGMA+ products only in LI animals. Furthermore, a higher amount of RGMA was found in the retinae of ONC + LI rats compared to ONC rats.

CONCLUSIONS:

Although a difference in the localization of RGMA is not obvious, the difference in the amount of RGMA is striking, the higher amount of RGMA in the retinae of ONC + LI rats compared to ONC rats indicates a role for RGMA during degeneration/regeneration processes. Our results are consistent with several reported neuroprotective effects of RGMA. Our new data showing the upregulation of RGMA after ONC in our regenerating model (plus LI) confirm these findings conducted in different settings.

• Authors: Sven Schnichels, Peter Heiduschka, Sylvie Julien
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 250 Issue 1 Pg. 39-50 (Jan 2012) ISSN: 1435-702X [Electronic] Germany
• PMID: 21887516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• GPI-Linked Proteins
• Glial Fibrillary Acidic Protein
• Membrane Proteins
• Nerve Tissue Proteins
• RGMA protein, rat
• neogenin

Topics

• Animals
• Antigens, CD (metabolism)
• Axons (metabolism)
• Blotting, Western
• Eye Injuries (metabolism)
• Fluorescent Antibody Technique, Indirect
• GPI-Linked Proteins
• Glial Fibrillary Acidic Protein (metabolism)
• Lens, Crystalline (injuries)
• Male
• Membrane Proteins (metabolism)
• Nerve Crush
• Nerve Tissue Proteins (metabolism)
• Neuroglia (metabolism)
• Optic Nerve Injuries (metabolism)
• Rats
• Rats, Wistar
• Retina (metabolism)
• Retinal Ganglion Cells (metabolism)