TY - JOUR
T1 - Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats
AU - Quigley, H. A.
AU - McKinnon, S. J.
AU - Zack, D. J.
AU - Pease, M. E.
AU - Kerrigan-Baumrind, L. A.
AU - Kerrigan, D. F.
AU - Mitchell, R. S.
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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 PPO (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 in glaucoma.
AB - 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 PPO (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 in glaucoma.
UR - http://www.scopus.com/inward/record.url?scp=0033775475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033775475&partnerID=8YFLogxK
M3 - Article
C2 - 11006239
AN - SCOPUS:0033775475
SN - 0146-0404
VL - 41
SP - 3460
EP - 3466
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 11
ER -