Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury

Abstract

Purpose: 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.

Figure 1.

Morphologic comparison of the retinas and optic nerves from normal cats, cats that received an optic nerve crush and no treatment (NT), or those that received either a single intravitreal injection of BDNF (eye), or the injection combined with 1 or 2 weeks of continuous infusion of BDNF into the visual cortex (eye+cortex).

Figure 2.

Comparison of mean ganglion cell survival under each experimental condition tested. Solid line: the mean number of cells counted in the normal fellow eyes. Mean ± SE (NT versus N: P < 0.001; Eye versus NT: P < 0.05; Eye+Ctx versus Eye: 1 week, NS; 2 week, P < 0.05; Eye+Ctx versus N: P > 0.05).

Figure 3.

Size distributions of ganglion cells in the experimental (top) vs. normal fellow (bottom) eyes as a percentage of the total number of ganglion cells in the sample region.

Figure 4.

PERG responses to visual stimuli of different spatial frequencies under each experimental condition. At 1 week, treatment of both the eye and eye+cortex is comparable to normal (A), whereas after a 2-week survival period, only the responses from animals receiving treatment of both the eye and cortex are normal (B). Mean ± SE.