Retrograde axonal transport obstruction of brain‐derived neurotrophic factor (BDNF) and its TrkB receptor in the retina and optic nerve of American Cocker Spaniel dogs with spontaneous glaucoma

Abstract

To determine the degree of retrograde optic nerve axonal transport obstruction at the scleral lamina cribosa level by examining levels of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor type B (TrkB) in dogs presenting with high intraocular pressure. A total of 10 eyes, four normal and six glaucomatous eyes, from normal and affected American Cocker Spaniels with primary glaucoma were studied. All eyes were assessed by neuro-ophthalmic examination, tonometry, gonioscopy, slit-lamp biomicroscopy, and indirect ophthalmoscopy prior to enucleation. Immunocytochemistry analysis was performed to evaluate BDNF and TrkB receptor expression in retina and optic nerve in normal and glaucomatous dogs. In all normal eyes BDNF immunostaining was detected in the cytoplasm of retinal ganglion cells (RGC), inner plexiform layer (IPL), inner nuclear layer (INL), nerve fiber layer (NFL), optic nerve head cells, and lamina cribosa cells. In all glaucomatous eyes BDNF was more evident in RGC, NFL and lamina cribosa cells. TrkB receptor was detected in the cytoplasm of RGC, NFL and ONH bundles in all normal eyes, and in a more intense pattern in all glaucomatous eyes. BDNF retrograde axonal transport is substantially inhibited by intraocular pressure elevation. TrkB accumulation at the ONH in glaucoma suggests a role for neurotrophin deprivation in the pathogenesis of RGC death in canine glaucoma, as well as a possible paracrine and/or autocrine signaling within the lamina cribosa. Neurotrophin signaling may regulate more than neuronal development, survival and differentiation. BDNF neurotrophin and its TrkB receptor expression by lamina cribosa cells and ONH astrocytes in glaucomatous eyes may help to determine the role of these cells as a paracrine source in terms of retinal ganglion cell survival, during episodes of elevated intraocular pressure.