Erythropoietin promotes survival of retinal ganglion cells in DBA/2J glaucoma mice.
OBJECTIVE
Retinal ganglion cell (RGC) loss occurs in response to increased intraocular pressure (IOP) and/or retinal ischemia in glaucoma and leads to impairment of vision. This study was undertaken to test the efficacy of erythropoietin (EPO) in providing neuroprotection to RGCs in vivo.


METHODS
The neuroprotective effects of EPO were studied in the DBA/2J mouse model of glaucoma. Mice were intraperitoneally injected with control substances or various doses of EPO, starting at the age of 6 months and continuing for an additional 2, 4, or 6 months. RGCs were labeled retrogradely by a gold tracer. IOP was measured with a microelectric-mechanical system, and EPO receptor (EPOR) expression was detected by immunohistochemistry. Axonal death in the optic nerve was quantified by para-phenylenediamine staining, and a complete blood count system was used to measure the number of erythrocytes.


RESULTS
In DBA/2J mice, the average number of viable RGCs significantly decreased from 4 months to 10 months, with an inverse correlation between the number of dead optic nerve axons and viable RGCs. Treatment with EPO at doses of 3000, 6000, and 12,000 U/kg body weight per week all prevented significant RGC loss, compared with untreated DBA/2J control animals. EPO effects were similar to those of memantine, a known neuroprotective agent. IOP, in contrast, was unchanged by both EPO and memantine. Finally, EPOR was expressed in the RGC layer in both DBA/2J and C57BL/6J mice.


CONCLUSIONS
EPO promoted RGC survival in DBA/2J glaucomatous mice without affecting IOP. These results suggest that EPO may be a potential therapeutic neuroprotectant in glaucoma.
Zhong
Lichun
L
(OSI) Eyetech, Inc., Lexington, Massachusetts, USA.
Bradley
John
J
Schubert
William
W
Ahmed
Ednan
E
Adamis
Anthony P
AP
Shima
David T
DT
Robinson
Gregory S
GS
Ng
Yin-Shan
YS
D000818:Animals; D001369:Axons / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007429:Intraocular Pressure / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D008559:Memantine