Minocycline prevents early axoglial alterations of the optic nerve induced optic induced by experimental glaucoma.

MELINA P BORDONE; MARÍA F GONZALEZ FLEITAS; LAURA A PASQUINI; ALEJANDRA BOSCO; PABLO H SANDE; RUTH ESTELA ROSENSTEIN; DAMIAN DORFMAN

Buenos Aires

Congreso; FALAN; 2016

Federation of Latin American and Caribbean Neuroscience Societies (FALAN) y Sociedad Argentina de Investigación en Neurociencias (SAN)

Abstract: Glaucoma is a leading cause of blindness, characterized byretinal ganglion cell (RGC) loss and optic nerve (ON) damage. Cumulativeevidence suggests the participation of glial cells in the degeneration ofthe ON and RGCs. We analyze the effect of minocycline on early axoglialalterations of the ON in an experimental model of glaucoma induced bychondroitin sulfate (CS) injections. For this purpose, vehicle or CS wereweekly injected into the eye anterior chamber from Wistar rats fordifferent intervals. A significant decrease in Brn3a(+) RGC number wasobserved in eyes injected with CS for 10 and 15 (but not 6) weeks. Areduction in anterograde transport of β-subunit cholera toxin (CTB) wasobserved in the superior colliculus and the lateral geniculate nucleuscontralateral to CS-injected eyes for 6 and 15 weeks. A disruption of CTBtransport was observed at the proximal myelinated ON. A significantdecrease in phosphorylated neurofilament heavy chain (pNFH)-immunoreactivity, an increase in Iba-1(+), ED1(+) (microglial markers),and glial fibrillary acidic protein (GFAP, astrocytes) (+) area, andsigns of demyelination were observed in the ON at 6 and 15 weeks ofocular hypertension. Microglial reactivity involvement was examinedthrough a daily treatment with minocycline (30 mg/kg, i.p.) for 2 weeks,after 4 weeks of ocular hypertension. Minocycline prevented the increasein Iba-1(+), ED-1(+), and GFAP(+) area, the decrease in pNFHimmunoreactivityand myelination, and the deficit in anterogradetransport induced by 6 weeks of ocular hypertension. Thus, minocyclinemight prevent early axoglial alterations in the glaucomatous proximal ON.