We have developed an improved low viscosity medium that provides rigid lumenal microvascular castings with minimal artifactual or agonal changes in lumenal diameter. By injecting this medium in rabbits under controlled physiologic conditions and carefully studying the resulting castings with the scanning electron microscope, we have measured and documented statistically significant changes in the diameters of ciliary blood vessels after topical application of several different adrenergic agents, many of them commonly used as chronic glaucoma therapy. Because these same drugs have also been shown by other investigators to significantly affect perfusion, we believe the vasomotor changes documented by our method are sufficient to affect ciliary blood flow. We propose to continue these studies by evaluating the vasomotor responses of the rabbit ciliary body to acutely and chronically administered adrenergic agents. We will then extend these experiments to the primate eye, using acute administration of agents that had a maximal effect on the rabbit eye. We will evaluate mechanisms of adrenergic vasomotor tone in the ciliary body by determining the interactions of commonly used adrenergic drug combinations in normal eyes and by studying the effects f adrenergic agents on the ciliary microvasculature of sympathectomized eyes. We will also use this technique to study the vasomotor characteristics of the optic nerve head. Thee investigations are of immediate clinical relevance, because regional alterations in perfusion may contribute to glaucomatous optic nerve damage and such alterations may be exacerbated by some of the adrenergic drugs prescribed to diminish the intraocular pressure. We will study the vascular anatomy of the optic disk in primates and other laboratory animals, with special attention to the presence of precapillary, arterial constrictions that may represent sphincters responsible for controlling optic disc perfusion. We will then (1) study the optic nerve head's response to vasoactive drugs by analyzing optic nerve casts of monkey and rabbit eyes from the above ciliary body experiments and (2) analyze casts from monkey and cat eyes with unilateral elevation of intraocular pressure to determine the anatomic site of optic nerve head autoregulation.
| 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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