Loss of photoreceptors that is reflected in a decline in visual capacity occurs in aging and one particularly severe manifestation of this is age-related macular degeneration (AMD). It is clear that in both aging and AMD, changes in the outer retina are occurring; however, the primary defect or defects underlying these changes are unclear. We propose to examine the effect of aging on the choroid and its neural regulation and determine if choroidal dysfunction is correlated with retinal pathology. We will use pigeons in these studies. Pigeons exhibit many of the same age-related visual changes as humans. They are a favorable animal in which to study age-related changes in neural control of choroidal blood flow because, extensive anatomical and physiological data on the neural circuits that controls choroidal blood flow in young pigeons (less than 1 yr) is available. Four different age groups of pigeons will be used (ranging from 1 to greater than or equal to 7 yrs, corresponding to 6 to greater than or equal to 50 years of age in humans. To explore the effect of aging on the choroid we will: 1) determine if basal choroidal blood flow is progressively altered with aging, using laser Doppler techniques; 2) determine if the distribution, abundance, or ultrastructural characteristics of the choroidal and choriocapillaris vascular beds are altered with aging; and 3) determine if the permeability of normally restricted serum proteins is altered in the choriocapillaris with aging. Additional studies will investigate whether the neural regulation of choroidal blood flow is altered in aging since, blood flow in the choroid is known to be under neural control by various types of peripheral sensory and autonomic fibers that adaptively regulate the choroidal blood flow in response to retinal need. We will examine the distribution of sensory and autonomic nerve fibers in the choroid in the different aged pigeons and the morphological and functional integrity of one specific neural circuit (the suprachiasmatic (SCN) - Edinger-Westphal (EW) - ciliary ganglion (CG) circuit) that has been implicated in the light-mediated reflexive control in choroidal blood flow will also be investigated. Alteration in adaptive regulation of the choroid may occur in aging, and these alterations may underlie the observed changes in photoreceptors. Finally, we will explore the possibility that changes in choroidal blood flow are correlated with photoreceptor loss in aged pigeons by correlating the physiological and functional data obtained on each animal with its data on the photoreceptors. This will be accomplished by analysis of retina at both the light and electron microscopic level, and also using morphometric techniques to determine the number and type of photoreceptors lost or affected. These experiments will provide information on the effect choroidal changes in aging may have on retinal health, which might allow a better understanding of the drastic effects of aging on photoreceptors.
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