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Abstract #17440 Published in IGR 9-2
Retinal ganglion cell protection by 17-beta-estradiol in a mouse model of inherited glaucoma
Zhou X; Li F; Ge J; Sarkisian Jr SR; Tomita H; Zaharia A; Chodosh J; Cao WDevelopmental neurobiology 2007; 67: 603-616
Glaucoma is the second leading cause of blindness in the world. The ultimate cause of vision loss due to glaucoma is thought to be retinal ganglion cell (RGC) apoptosis. Neuroprotection of RGC is becoming an important approach of glaucoma therapy. Several lines of evidence suggest that estrogen has neurotrophic and neuroprotective properties. In this study, we examine the role of estrogen in preventing RGC loss in DBA/2J mouse, an in vivo model of an inherited (pigmentary) glaucoma. Two-month-old female DBA/2J mice were anesthetized and ovariectomized with or without subcutaneous 17beta-estradiol (βE2) pellet implantation. RGC survival was evaluated from flat-mounted whole retinas by counting retrograde-labeled cells. The loss of nerve fibers and RGC were also evaluated in paraffin-fixed retinal cross sections. Biochemical alterations in the retinas of DBA/2J mice in response to systemic injection of βE2 were also examined. We have made several important observations showing that: (1) βE2 treatment reduced the loss of RGC and neurofibers through inhibition of ganglion cell apoptosis, (2) βE2 activated Akt and cAMP-responsive-element-binding-protein (CREB), (3) βE2 up-regulated thioredoxin-1 (Trx-1) expression, (4) βE2 reduced the increased activations of mitogen-activated protein kinases (MAPK) and NF-κB, (5) βE2 inhibited the increased interleukin-18 (IL-18) expression, and (6) treatment with tamoxifen, an estrogen receptor antagonist, blocked βE2-mediated activation of Akt and inhibition of MAPK phosphorylation in the retinas of DBA/2J mice. These findings suggest the possible involvement of multiple biochemical events, including estrogen receptor/Akt/CREB/thioredoxin-1, and estrogen receptor/MAPK/NF-κB, in estrogen-mediated retinal ganglion cell protection.
Dr. X. Zhou, Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)