Abstract
Abstract: :
Purpose: Retinal ganglion cell degeneration due to pressure-induced damage to the optic nerve is considered the basis for glaucomatous optic neuropathy. Previous work in our laboratory has suggested that brain-derived neurotrophic factor (BDNF) is an effective neuroprotectant in primate-sized eyes, but that it might not affect all classes of ganglion cells equally. The purpose of this study was to examine the effects that optic nerve injury and intravitreal treatment with BDNF have on alpha and beta type ganglion cells in the cat retina. Methods: An isolated, living, retina preparation and intracellular injection techniques were used to label the somata and dendritic arbors of single ganglion cells in retinae of normal cats, cats that received unilateral optic nerve crush alone, and those receiving optic nerve crush and treatment of the affected eye with a single, intravitreal, injection of BDNF (30µg) at the time of the nerve injury; this dose of BDNF was found previously by us to provide the greatest level of neuroprotection in the cat eye. Labeled neurons (25-30/condition/cell class) were reconstructed and analyzed using confocal microscopy and Neurolucida cell analyses software. Results: Optic nerve crush alone results in a significant (~30%; p<0.05; 2-tailed t-test) decrease in the mean soma sizes of both alpha and beta cells. While beta cell somata in retinae treated with BDNF were not significantly different in size from those following optic nerve crush alone, the mean soma sizes of alpha cells in these same retinae were only 5% smaller than normal. The dendritic fields of alpha, but not beta, cells were significantly smaller than normal following optic nerve crush (48% vs 19% reduction in mean area). Following BDNF treatment, the dendritic field sizes of both alpha and beta cells were not significantly different from normal (p>0.05). As with dendritic field area, alpha cells also showed more significant changes with respect to dendritic surface area, number of branch points, and dendritic complexity, based on Sholl analyses. In all cases, these features were found not to be significantly different from normal following treatment with BDNF. Conclusions: The data indicate that the somata and dendritic fields of surviving alpha and beta cells are affected differentially by optic nerve injury. In general, alpha cells appear to be affected more severely, but they also show a greater response to the neuroprotective effects of BDNF. These differential effects might reflect differences in the number and type (full length vs truncated) of high affinity BDNF receptors (TrkB) on alpha vs beta cells.
Keywords: neuroprotection • ganglion cells • anatomy