Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis.
Optic neuritis is inflammation of the optic nerve and is strongly associated with multiple sclerosis (MS), an inflammatory demyelinating syndrome of the central nervous system. It leads to retinal ganglion cell (RGC) death and can cause severe vision loss. Brimonidine (BMD) is a selective α2-adrenergic receptor agonist that is used clinically for the treatment of glaucoma. BMD lowers intraocular pressure, but recent evidence suggests that its therapeutic efficacy may also mediate through mechanisms independent of modulation of intraocular pressure. In this study, we examined the effects of topical administration of BMD on retinal degeneration during optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE was induced with MOG35-55 in C57BL/6J mice and BMD eyedrops were applied daily. In the EAE retina, the number of RGCs was significantly decreased and this effect was suppressed with BMD treatment. Consistent with histological analyses, the visual impairment observed in EAE mice was inhibited with BMD treatment, indicating the functional significance of the neuroprotective effect of BMD. Furthermore, BMD increased the expression level of basic fibroblast growth factor in the EAE retina, particularly in Müller glial cells and RGCs. Our findings suggest that topical administration of BMD may be available for RGC protection during optic neuritis, as well as for glaucoma.
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Xiaoli
X
Guo
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Kazuhiko
K
Namekata
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Atsuko
A
Kimura
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Takahiko
T
Noro
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Yuriko
Y
Azuchi
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Kentaro
K
Semba
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Chikako
C
Harada
Department of Neuro-ophthalmology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan.
Hiroshi
H
Yoshida
Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Yoshinori
Y
Mitamura
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; Department of Neuro-ophthalmology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan. Electronic address: harada-tk@igakuken.or.jp.
Takayuki
T
Harada
D060433:Administration, Ophthalmic; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000068438:Brimonidine Tartrate; D005260:Female; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009883:Ophthalmic Solutions; D009902:Optic Neuritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology* / Q000627:therapeutic use; D055351:Retinal Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D058647:Adrenergic alpha-2 Receptor Agonists; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D000068438:Brimonidine Tartrate
Brimonidine; Demyelination; EAE; Neuroprotection; Optic neuritis