Glaucoma is a chronic neurodegeneration characterized functionally by initial loss of peripheral vision that may progress to blindness and structurally by loss of retinal ganglion cells (RGCs) and optic nerve axons. Clinical measurement of function is performed by subjective perimetry (visual fields), and measurement of structure loss is performed by direct optic nerve examination and assessment of longitudinal changes in color fundus photographs. Major risk factors for glaucoma include age, race, and intraocular pressure (IOP). IOP is the only FDA-approved factor amenable to modification with topical or oral medications, laser or surgery. Current research efforts are directed at earlier diagnosis and improved therapy. Standard automated perimetry does not detect functional damage until up to 50% of RGCs are lost, so newer tests target specific RGC subsystems such as magnocellular, parvocellular and motion-sensitive pathways. Wide variation in the appearance of optic nerves makes clinical evaluation highly subjective, so efforts have focused on objective measurements of retinal and optic nerve damage. Loss of RGC axons in the retina can be detected by scanning laser polarimetry and optical coherence tomography (OCT), and changes in optic nerve head topography can be detected by confocal scanning laser. Improvements in imaging involve the combination of adaptive optics and spectral-domain OCT, and polarization-sensitive OCT. Improvements in therapy involve drugs targeting extracellular matrix in the aqueous outflow system and novel surgical devices, and neuroprotective and regenerative strategies unrelated to IOP lowering. With these advances we hope to delay or prevent glaucoma, a leading causes of vision loss world-wide.
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.
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