Age-related decline in VIP-positive parasympathetic nerve fibers in the human submacular choroid.

PURPOSE An age-related decline in macular choroidal blood flow (ChBF) occurs in humans. Vasodilatory nerve fibers containing vasoactive intestinal polypeptide (VIP) innervate choroidal blood vessels. The current study was conducted to examine the possibility that an age-related loss of these fibers might occur in the submacular choroid in humans, and thus contribute to a decline in ChBF. METHODS Macular choroid punches were collected from 35 healthy human donors ranging from 21 to 93 years of age. Choroidal samples were immunolabeled using anti-VIP and the peroxidase-antiperoxidase METHOD VIP-positive nerve fiber abundance was quantified in up to 12 fields per punch. Fifty macular punches were analyzed, and results for eye pairs were averaged. Choroidal vessel diameter (ChVD) was measured for these same fields. The relationship between age and vessel diameter or VIP-positive fiber abundance was analyzed. Multivariate statistical models were generated correcting for gender, variables related to the tissue specimens, and potential procedural sources of variability. RESULTS The fully adjusted multivariate models showed a significant age-related reduction in both the VIP-positive fiber abundance (P = 0.0003, adjusted R(2) = 0.51) and ChVD (P < 0.0001, adjusted R(2) = 0.63), with slopes of -0.45 and -0.19, respectively. Adjusting for the same variables, VIP-positive fiber abundance showed a significant direct correlation with ChVD. CONCLUSIONS The results indicate a significant age-related decline in VIP-positive nerve fibers and vessel diameter in the submacular choroid in disease-free human donor eyes. These findings suggest that a decline in the neural control of ChBF and vessel diameter may explain the reductions in ChBF and its adaptive control observed clinically with aging.