Dear Lin,

I hope that enclosed paper will be helpful for your reasearch .

Good Luck !

Graefes Arch Clin Exp Ophthalmol. 2014 May;252(5):761-72. doi: 10.1007/s00417-014-2588-4. Epub 2014 Feb 25.

Minocycline upregulates pro-survival genes and downregulates pro-apoptotic genes in experimental glaucoma.

Levkovitch-Verbin H1, Waserzoog Y, Vander S, Makarovsky D, Piven I.

Author information

1Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, [email protected].

Abstract

PURPOSE:

Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, was reported to be neuroprotective in experimental glaucoma and optic nerve transection as well as in other neurodegenerative diseases. The purpose of this study was to investigate the mechanism underlying that neuroprotective effect in murine glaucoma.

METHODS:

Elevated intraocular pressure was induced in 159 rats by the translimbal photocoagulation laser model. Minocycline 22 mg/kg or saline was injected intraperitoneally starting 3 days before the induction of glaucoma, and continued daily until the animals were sacrificed. The effect of minocycline on gene expression was evaluated using a quantitative polymerase chain reaction (PCR) array for apoptosis. The involvement of selected pro-apoptotic, pro-survival, and inflammatory genes was further analyzed by quantitative real-time PCR at multiple time points. Immunohistochemistry was used to study the effect of minocycline on microglial activation and to localize Bcl-2 changes.

RESULTS:

Minocycline significantly increased the anti-apoptotic gene Bcl-2 expression at day 8 and day 14 after the induction of glaucoma (p = 0.04 and p = 0.03 respectively), and decreased IL-18 expression in the retina at day 14 and day 30 (p = 0.04 and p 

Dear Lin,

I hope that another enclosed paper will be helpful for your reasearch .

Good Luck !

Dis Model Mech. 2015 May;8(5):443-55. doi: 10.1242/dmm.018788. Epub 2015 Mar 9.

Neurodegeneration severity can be predicted from early microglia alterations monitored in vivo in a mouse model of chronic glaucoma.

Bosco A1, Romero CO2, Breen KT2, Chagovetz AA3, Steele MR2, Ambati BK4, Vetter ML2.

Author information

1Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA [email protected].

2Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.

3Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA.

4Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132, USA.

Abstract

Microglia serve key homeostatic roles, and respond to neuronal perturbation and decline with a high spatiotemporal resolution. The course of all chronic CNS pathologies is thus paralleled by local microgliosis and microglia activation, which begin at early stages of the disease. However, the possibility of using live monitoring of microglia during early disease progression to predict the severity of neurodegeneration has not been explored. Because the retina allows live tracking of fluorescent microglia in their intact niche, here we investigated their early changes in relation to later optic nerve neurodegeneration. To achieve this, we used the DBA/2J mouse model of inherited glaucoma, which develops progressive retinal ganglion cell degeneration of variable severity during aging, and represents a useful model to study pathogenic mechanisms of retinal ganglion cell decline that are similar to those in human glaucoma. We imaged CX3CR1(+/GFP) microglial cells in vivo at ages ranging from 1 to 5 months by confocal scanning laser ophthalmoscopy (cSLO) and quantified cell density and morphological activation. We detected early microgliosis at the optic nerve head (ONH), where axonopathy first manifests, and could track attenuation of this microgliosis induced by minocycline. We also observed heterogeneous and dynamic patterns of early microglia activation in the retina. When the same animals were aged and analyzed for the severity of optic nerve pathology at 10 months of age, we found a strong correlation with the levels of ONH microgliosis at 3 to 4 months. Our findings indicate that live imaging and monitoring the time course and levels of early retinal microgliosis and microglia activation in glaucoma could serve as indicators of future neurodegeneration severity.

Thanks, Marianne.