Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.
OBJECTIVE
To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone.


METHODS
Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally.


RESULTS
Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so.


CONCLUSIONS
Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.
Weber
Arthur J
AJ
Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA. weberar@msu.edu
Viswanáthan
Suresh
S
Ramanathan
Chidambaram
C
Harman
Christine D
CD
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002415:Cats; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D007267:Injections; D008297:Male; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020221:Optic Nerve Injuries / Q000503:physiopathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012162:Retinal Degeneration / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects*; D014822:Vitreous Body / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D011994:Recombinant Proteins