May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Erythropoietin Promotes Survival of Retinal Ganglion Cells in the DBA/2J Glaucoma Mouse model
Author Affiliations & Notes
  • L. Zhong
    Research, (OSI), Lexington, MA
  • J. Bradley, Sr.
    Research, (OSI), Lexington, MA
  • A. Adamis, Sr.
    Research, (OSI), Lexington, MA
  • D. Shima
    Research, (OSI), Lexington, MA
  • Y.–S. Ng, Sr.
    Research, (OSI), Lexington, MA
  • G. Robinson
    Research, (OSI), Lexington, MA
  • Footnotes
    Commercial Relationships  L. Zhong, (OSI) eyetech Pharmaceuticals Inc., E; J. Bradley, (OSI) eyetech Pharmaceuticals Inc., E; A. Adamis, (SOI) eyetech Pharmaceuticals Inc., E; D. Shima, (OSI)eyetech Pharmaceuticals Inc., E; Y. Ng, (OSI)eyetech Pharmaecuticals Inc., E; G. Robinson, (OSI)eyetech Pharmaceuticals Inc., E.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1574. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      L. Zhong, J. Bradley, Sr., A. Adamis, Sr., D. Shima, Y.–S. Ng, Sr., G. Robinson; Erythropoietin Promotes Survival of Retinal Ganglion Cells in the DBA/2J Glaucoma Mouse model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1574.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : In glaucoma, increased intraocular pressure (IOP) and/or retinal ischemia results in retinal ganglion cell (RGC) loss and impaired vision. Erythropoietin (Epo) has been indicated to be an effective neuroprotectant for neuronal cells including RGCs. In this study, we established whether Epo provides neuroprotection to RGCs in the murine DBA/2J spontaneous glaucoma model.

Methods: : DBA/2J mice were treated with BSA (0.1% in PBS 300µL/injection/wk), memantine (70 mg/kg BW/wk), or Epo (3,000, 6,000 and 12,000 units/kg BW/wk) by intraperitoneal (i.p.) injection. Non–treated DBA/2J and C57BL/6J mice served as experimental controls. Treatment was initiated at 6 months of age and continued for an additional 2, 4 or 6 months. IOP was measured before and after each treatment, and RGCs were labeled by retrograde transport following injection of FluoroGold dye into the superior colliculus. Retinal flat–mounts were prepared and 8 fluorescent images per retina (16 images per mouse) were captured of the area between the optic nerve and the peripapillary region. The number of living RGCs was determined using the Fovea Pro plug–in (Reindeer Graphics) in Adobe Photoshop. Retinal expression of the Epo receptor (EpoR) was evaluated by immunohistochemistry. Dead axons in the optic nerve were quantified by Para–phenylenediamine (PPD) staining.

Results: : RGC loss was determined in DBA/2J mice by retrograde fluorogold labeling. Compared with mice at the age of 6 months, RGC loss increased at 8 (15.84 %), 10 (33.87 %), and 12 (54.77 %) months of age, and was significantly greater than observed in C57BL/6J controls. PPD staining from different age groups revealed a robust inverse correlation between the numbers of dead axons and living RGCs. DBA/2J mice treated with Epo at 6,000 units/kg BW/wk for 4 months showed a statistically significant increase in erythrocytes (16.10 million/µL) as compared to DBA/2J mice treated with 0.1% BSA (9.87 million/µL). However, Epo at 3,000, 6,000 and 12,000units/kg BW/wk for 2, 4 or 6 months did not decrease IOP in the DBA/2J mice. Compared with untreated DBA/2J retinas, Epo treatment at 3,000–12,000 units/kg BW/wk increased the number of RGCs at 4 and 6 months post–treatment. Epo–mediated RGC protective effects were similar in magnitude to those observed for memantine. EpoR expression in the RGC layer suggested a direct response to Epo treatment

Conclusions: : Epo treatment inhibited RGC apoptosis and promoted survival of RGCs in DBA/2J spontaneous glaucoma mice. This result suggests that Epo may be a potential therapeutic neuroprotectant for RGCs in glaucoma patients.

Keywords: retinal degenerations: cell biology • apoptosis/cell death • drug toxicity/drug effects 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×