Effects of minocycline on apoptosis and neuronal changes in retinal ganglion cells from experimental optic neuritis rats

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Abstract

BACKGROUND:

Minocycline, a tetracycline derivative, is neuroprotective in models of various neurological diseases.

OBJECTIVE:

To investigate the effects of minocycline on retinal ganglion cells (RGCs) in rats with optic neuritis, and to compare with the effects of methylprednisolone.

DESIGN, TIME AND SETTING:

This neuropathology controlled study was performed at the First Affiliated Hospital, Chongqing Medical University, China in May 2007.

MATERIALS:

A total of 22 female Wistar rats were randomly assigned into a normal control group (n = 5) and an experimental group (n = 17). The experimental group was composed of a model subgroup (n = 7), a minocycline subgroup (n = 5), and a methylprednisolone subgroup (n = 5). Minocycline was supplied by Sigma, USA.

METHODS:

Antigen homogenate made from guinea pig spinal cord and complete Freund adjuvant was used to induce autoimmune encephalomyelitis, which could induce demyelinated optic neuritis models. Rats in the minocycline subgroup were intraperitoneally injected with minocycline (45 mg/kg) daily from day 8 following autoimmunity. Rats in the methylprednisolone subgroup were intraperitoneally injected with methylprednisolone (20 mg/kg) daily from day 8 following autoimmunity.

MAIN OUTCOME MEASURES:

On day 18 after autoimmunity induction, pathological changes in the optic nerve were observed by hematoxylin-eosin staining. The percentage area of axons in the transverse section of the optic nerve was measured by Bielschowsky staining. Apoptosis of RGCs was detected by TUNEL.

RESULTS:

Under an optical microscope, the optic nerve in rats with demyelinated optic neuritis showed a vacuole-like structure of fibers, irregular swelling of the axons, and infiltration of a large quantity of inflammatory cells. With an electron microscope, the optic nerve presented with vacuole-like structures in the axons, a small percentage area of axons in the transverse section, loose myelin sheaths, and microtubules and microfilaments disappeared. The pathological changes in the optic nerve met the changes in demyelinated optic neuritis. Moreover, there was significant apoptosis of RGCs. The percentage area of optic nerve axons in the transverse section was significantly increased and the number of apoptotic RGCs was increased after treatment with methylprednisolone and minocycline. Compared with methylprednisolone, minocycline had better effects on reducing RGC apoptosis (P < 0.05).

CONCLUSION:

Minocycline has better inhibitory effects on RGC apoptosis than methylprednisolone. Minocycline can decrease the damage to axons of demyelinated optic neuritis rats, and has similar protective effects on neurons from demyelinated optic neuritis rats as methylprednisolone.

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