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Harry A. Quigley, Stuart J. McKinnon, Donald J. Zack, Mary Ellen Pease, Lisa A. Kerrigan–Baumrind, Danielle F. Kerrigan, Rebecca S. Mitchell; Retrograde Axonal Transport of BDNF in Retinal Ganglion Cells Is Blocked by Acute IOP Elevation in Rats. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3460-3466.
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purpose. To determine whether acute experimental glaucoma in rats obstructs
retrograde transport of brain-derived neurotrophic factor (BDNF) to
retinal ganglion cells (RGCs).
methods. Forty rats had unilateral injection of either 125I-BDNF (20
animals) or a mixture of 125I-BDNF and 100-fold excess
nonradiolabeled BDNF (20 animals). In each group of 20 animals, eyes
contralateral to injection had either normal intraocular pressure (IOP;
10 animals) or IOP elevated to 25 mm Hg below the systolic blood
pressure of the eye (10 animals). In each group of 20 rats, ipsilateral
eyes had IOP set at systolic blood pressure (4 eyes), had optic nerve
transection (10 eyes), or had normal IOP (6 eyes). Six hours after
injection, animals were killed and tissues were fixed, embedded, and
sectioned for autoradiography. Grain counts were performed over retina
and optic nerve using automated image analysis.
results. IOP elevation to 25 mm Hg below systolic blood pressure (perfusion
pressure [PP] 25) decreased median retinal nerve fiber layer (NFL)
grains by 38% compared with controls (P < 0.001).
Competition by cold BDNF reduced NFL grains by 28%
(P = 0.013). Considering only the radioactivity
representing specific retrograde transport of BDNF, IOP elevation to
PP25 reduced transport by 74%, whereas elevation to PP0 (equaling
systolic blood pressure) reduced specific transport by 83%.
conclusions. BDNF is transported retrogradely from the superior colliculus in adult
rats, and this transport is substantially inhibited by acute IOP
elevation. Deprivation of BDNF among RGCs may contribute to neuron loss
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