Retrograde Axonal Transport of BDNF in Retinal Ganglion Cells Is Blocked by Acute IOP Elevation in Rats

• Published in: Investigative ophthalmology & visual science Vol. 41; no. 11; pp. 3460 - 3466
• Main Authors: Quigley, Harry A, McKinnon, Stuart J, Zack, Donald J, Pease, Mary Ellen, Kerrigan-Baumrind, Lisa A, Kerrigan, Danielle F, Mitchell, Rebecca S
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01-10-2000; Association for Research in Vision and Ophtalmology
• Subjects: Acute Disease; Animals; Autoradiography; Axonal Transport; Biological and medical sciences; Blood Pressure; Brain-Derived Neurotrophic Factor - metabolism; Denervation; Glaucoma and intraocular pressure; Intraocular Pressure; Male; Medical sciences; Nerve Fibers - metabolism; Ocular Hypertension - metabolism; Ophthalmology; Optic Disk - metabolism; Optic Nerve - physiology; Optic Nerve - surgery; Rats; Rats, Inbred BN; Retinal Ganglion Cells - metabolism; Superior Colliculi - metabolism; Pathophysiology; Rat; Acute; Retrograde; Biological transport; Rodentia; Ocular hypertension; Axon; Retina; Experimental study; Ganglion; Eye disease; Vertebrata; Mammalia; Glaucoma (eye); Animal; Brain derived neurotrophic factor; Inhibition; Cell
• ISSN: 0146-0404; 1552-5783

To determine whether acute experimental glaucoma in rats obstructs retrograde transport of brain-derived neurotrophic factor (BDNF) to retinal ganglion cells (RGCs).
Forty rats had unilateral injection of either (125)I-BDNF (20 animals) or a mixture of (125)I-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.
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%.
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.