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C. F. Marfurt, L. Dvorscak, D. Ellch; Effect of Aging on Corneal Epithelial Nerve Density. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5656.
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Dry eye is a disorder of the tear film common in the elderly and is associated with altered composition or volume of tears, leading to ocular surface damage and ocular discomfort. The causes of dry eye in the aged population are numerous and multi-factorial; however, it is hypothesized that a major contributing factor is an age-related reduction in corneal sensitivity leading to impaired reflex tear secretion. The purpose of the current study is to determine the effect of aging on corneal epithelial nerve density in a rat model.
Fischer 344 rats aged 6, 12, 18, and 24 months were obtained from the National Institute of Aging. Whole corneas were immersion-fixed, permeabilized overnight in 1% hyaluronidase and stained immunohistochemically with a primary antibody against the pan-neuronal marker, beta-neurotubulin. Epithelial nerve densities were analyzed in 1mm-square areas from the central and perilimbal regions of the inferotemporal quadrant in each cornea. Line drawings of all stained nerves within each 1mm-square area were made with the aid of a drawing tube attached to a light microscope. By altering the plane of focus, separate composite drawings were made of the subbasal nerves and their distal terminal branches. The images were then scanned into a computer and nerve densities per square millimeter of corneal epithelium were calculated using Image J.
From 6 to 24 months, intraepithelial nerve terminal density in the central and peripheral cornea decreased by 38% and 27%, respectively. In marked contrast, from 6 to 24 months, subbasal nerve density in the same central and peripheral areas increased by 95% and 105%, respectively.
Epithelial nerve terminal density in the central and peripheral rat cornea decreases progressively and significantly between 6 and 24 months. The progressive loss of these nerve terminals, which represent the sensory transducer regions of the nerve fibers, provides a morphological explanation for the diminished sensitivity seen in aged individuals and may contribute to the increased incidence of dry eye. The dramatic and concurrent increase in corneal subbasal nerve density in older animals was an unexpected observation; however, because subbasal nerves may contain multiple axons, the true effect of aging on axon number in the subbasal plexus will need to be determined by electron microscopy.
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