The goal of the proposed research remains characterization of the peripheral innervation to the eye by integration of histochemical, anatomical and biochemical methods. We shall extend our recent studies of the intraocular distribution of nerve fibers producing nitric oxide to other species, shall seek evidence for novel isozymes of its biosynthetic enzyme and study the potential role of nitric oxide in retinal ischemia and corneal denervation. Continuing our longstanding study of intraocular peptidergic nerve fibers, we propose analysis that includes ocular and related cranial tissues and further searches for novel neuropeptides. We shall focus on the parasympathetic component of the ocular innervation as the most likely to the parasympathetic component of the ocular innervation as the most likely to provide novel insights for future physiologic and pharmacologic studies, not only continuing study of primary neural messengers but also addressing the intraocular distribution of receptors to selected parasympathetic messenger molecules. We also shall seek evidence for novel neuroregulatory or paracrine mechanisms in he eye. Using modern methods, we shall integrate findings in the eye with the neurochemical organization of the relevant cranial ganglia to achieve a comprehensive understanding of the peripheral innervation of the eye. Our identifications of the primary neural messengers and their interrelationships provide an essential basis for understanding the regulatory mechanisms that govern ocular physiology. Furthermore, given the importance of neural mechanisms in ocular pharmacology, such studies provide the basis for understanding ophthalmic drugs and developing novel clinical therapies. The breadth of our pharmacologic perspective and the versatility of our methods will continue to produce results relevant to the physiology and therapy of important ocular disorders, such as glaucoma, circulatory disease, injury and inflammation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005454-12
Application #
2159431
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-07-01
Project End
1999-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Grimes, P A; Lahiri, S; Stone, R et al. (1994) Nitric oxide synthase occurs in neurons and nerve fibers of the carotid body. Adv Exp Med Biol 360:221-4
Grimes, P A; McGlinn, A M; Koeberlein, B et al. (1994) Galanin immunoreactivity in autonomic innervation of the cat eye. J Comp Neurol 348:234-43
Lin, T; Grimes, P A; Stone, R A (1993) Expansion of the retinal pigment epithelium in experimental myopia. Vision Res 33:1881-5
Yamamoto, R; Bredt, D S; Snyder, S H et al. (1993) The localization of nitric oxide synthase in the rat eye and related cranial ganglia. Neuroscience 54:189-200
Yamamoto, R; Bredt, D S; Dawson, T M et al. (1993) Enhanced expression of nitric oxide synthase by rat retina following pterygopalatine parasympathetic denervation. Brain Res 631:83-8
Li, H; Grimes, P (1993) Adrenergic innervation of the choroid and iris in diabetic rats. Curr Eye Res 12:89-94
Iuvone, P M; Tigges, M; Stone, R A et al. (1991) Effects of apomorphine, a dopamine receptor agonist, on ocular refraction and axial elongation in a primate model of myopia. Invest Ophthalmol Vis Sci 32:1674-7
Stone, R A; Lin, T; Laties, A M (1991) Muscarinic antagonist effects on experimental chick myopia. Exp Eye Res 52:755-8
Yamamoto, R; McGlinn, A; Stone, R A (1991) Brain natriuretic peptide-immunoreactive nerves in the porcine eye. Neurosci Lett 122:151-3
Ye, X D; Laties, A M; Stone, R A (1990) Peptidergic innervation of the retinal vasculature and optic nerve head. Invest Ophthalmol Vis Sci 31:1731-7

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