title: Changes in optic nerve head blood flow, visual function, and retinal histology in hypercholesterolemic rabbits.
abstract: We investigated the effects of hypercholesterolemia on optic nerve head (ONH) blood flow, visual function, and retinal histology in a rabbit model. Hypercholesterolemia was induced in rabbits by feeding them a high cholesterol (1%) diet for 12 weeks. Changes in blood pressure, intraocular pressure (IOP), and ONH blood flow were monitored at 6 and 12 weeks after treatment. The autoregulation of ONH blood flow as detected by laser speckle flowgraphy was verified by an artificial elevation of IOP at 12 weeks. Visually evoked potentials (VEPs) were also recorded and analyzed at 6 and 12 weeks. Finally, a histological examination as well as immunohistochemistry to endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) was performed. In the hypercholesterolemic rabbits, blood pressure, IOP, and ONH blood flow did not alter significantly throughout this study. The autoregulation of ONH blood flow against IOP elevation was found to be impaired at 12 weeks. The amplitudes of the first negative peak of VEPs were diminished. Both the density of the retinal ganglion cells and the thickness of the inner nuclear layer and photoreceptor cell layer were reduced. Immunoreactivity to eNOS was reduced and that to iNOS was enhanced in the hypercholesterolemic rabbits compared to those in the normal control rabbits. The results of this study show that hypercholesterolemia induces impairment in the autoregulation of ONH blood flow and deterioration in visual function and histology. Downregulation of eNOS activity might be one of the causes for impairment of the autoregulation. Enhanced activity of iNOS might be involved in the impaired visual function and histology.
authors: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors: Maho
authors: M
authors: Shibata
authors: Tetsuya
authors: T
authors: Sugiyama
authors: Masaaki
authors: M
authors: Hoshiga
authors: Junko
authors: J
authors: Hotchi
authors: Takashi
authors: T
authors: Okuno
authors: Hidehiro
authors: H
authors: Oku
authors: Toshiaki
authors: T
authors: Hanafusa
authors: Tsunehiko
authors: T
authors: Ikeda
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002791:Cholesterol, Dietary / Q000097:blood; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual; D005123:Eye / Q000201:enzymology / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D006706:Homeostasis; D006937:Hypercholesterolemia / Q000150:complications* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007429:Intraocular Pressure; D017078:Laser-Doppler Flowmetry; D057066:Low Tension Glaucoma / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009898:Optic Disk / Q000098:blood supply*; D011817:Rabbits; D012039:Regional Blood Flow; D012165:Retinal Ganglion Cells / Q000201:enzymology / Q000473:pathology*; D013997:Time Factors; D014785:Vision, Ocular
chemical_list: D002791:Cholesterol, Dietary; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III