advertisement
Abstract #15858 Published in IGR 2-3
Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats
Quigley HA; McKinnon SJ; Zack DJ; Pease ME; Kerrigan-Baumrind LA; Kerrigan DF; Mitchell RSInvestigative Ophthalmology and Visual Science 2000; 41: 3460-3466
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 (125)I-BDNF (20 animals) or a mixture of (125)I-BDNF and 100-fold excess nonradiolabelled BDNF (20 animals). In each group of 20 animals, eyes contralateral to injection had either normal intraocular pressure (IOP; ten animals) or IOP elevated to 25 mmHg below the systolic blood pressure of the eye (ten animals). In each group of 20 rats, ipsilateral eyes had IOP set at systolic blood pressure (four eyes), had optic nerve transection (ten eyes), or had normal IOP (six 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 mmHg 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 (equalling 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.
Dr. H.A. Quigley, Glaucoma Research Laboratory, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. hquigley@jhmi.edu
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
