Using methylmethacrylate lumenal microvascular castings, we have detailed the vascular anatomy of the ciliary body and optic nerve head of non- primate mammals and non-human primates. We have extended this technique to evaluate the vasomotor response to a variety of vasoactive agents on microvascular beds in these tissue. Using this technique, we will now test the hypothesis that physiological and anatomical features of the primate optic nerve head vasculature make it susceptible to microcirculatory compromise. A better understanding of the vasomotor activity of the optic nerve vasculature is needed to evaluate its role in the development of glaucomatous optic neuropathy. The corrosion casting technique injects a low viscosity media into the vascular lumen, under physiologically controlled conditions, to produce a rigid replication of the microvascular beds, which can be examined with a scanning electron microscope. The technique induces minimal artifactual change and has been used to demonstrate the vasomotor activity of various adrenergic drugs, including some used in glaucoma therapy. We now plan to apply this technique to define further the normal vascular anatomy of the optic nerve in non-primate mammals (rabbits and raccoons), non-human primates (squirrel monkeys), and human cadaver eyes. We will also identify points of regional vasomotor control of the optic nerve and peripapillary vasculature, and we will establish the effects of endogenous, vasoactive agents (such as endothelins and nitric oxide) on these control points. Physiological stimuli (CO2, O2 and intraocular pressure) will be used to modify the optic nerve vascular supply and to confirm that the vascular changes seen in the pharmacological studies are compatible with the normal autoregulatory mechanisms. We will use endothelin, a potent regional vasoconstrictor produced by endothelial cells, to create a model of chronic optic nerve ischemia, initially in a lower mammal and then in a non-human primate. The ischemic changes produced in this model will be compared to optic nerve changes of glaucomatous optic neuropathy. We will attempt to block the ischemic consequences of endothelin with vasodilators, such as calcium channel blockers and transdermal nitrates. In addition, the effects of nitric oxide (an extracellular messenger which causes regional vasodilation) on the primate optic nerve vasculature will be determined, in the presence and absence of chronic ischemia. Finally, we will manipulate the unique venous outflow in the primate eye to understand its contribution to optic nerve head perfusion and possibly to ischemic changes.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Good Samaritan Hosp & Medical Center(Prtlnd,OR)
United States
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Fortune, Brad; Wang, Lin; Cull, Grant et al. (2008) Intravitreal colchicine causes decreased RNFL birefringence without altering RNFL thickness. Invest Ophthalmol Vis Sci 49:255-61
Wang, Lin; Fortune, Brad; Cull, Grant et al. (2007) Microspheres method for ocular blood flow measurement in rats: size and dose optimization. Exp Eye Res 84:108-17
Wang, Lin; Fortune, Brad; Cull, Grant et al. (2006) Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage. Arch Ophthalmol 124:717-24
Cioffi, George A (2005) Ischemic model of optic nerve injury. Trans Am Ophthalmol Soc 103:592-613
Fortune, Brad; Wang, Lin; Bui, Bang V et al. (2005) Idiopathic bilateral optic atrophy in the rhesus macaque. Invest Ophthalmol Vis Sci 46:3943-56
Cioffi, George A; Wang, Lin; Fortune, Brad et al. (2004) Chronic ischemia induces regional axonal damage in experimental primate optic neuropathy. Arch Ophthalmol 122:1517-25
Fortune, Brad; Bui, Bang V; Morrison, John C et al. (2004) Selective ganglion cell functional loss in rats with experimental glaucoma. Invest Ophthalmol Vis Sci 45:1854-62
Wang, Lin; Dong, Jin; Cull, Grant et al. (2003) Varicosities of intraretinal ganglion cell axons in human and nonhuman primates. Invest Ophthalmol Vis Sci 44:2-9
Cull, Grant; Cioffi, George A; Dong, Jin et al. (2003) Estimating normal optic nerve axon numbers in non-human primate eyes. J Glaucoma 12:301-6
Wang, Lin; Cioffi, George A; Cull, Grant et al. (2002) Immunohistologic evidence for retinal glial cell changes in human glaucoma. Invest Ophthalmol Vis Sci 43:1088-94

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