Влияние старения и пола на плотность и функцию роговичных нервов

The Impact of Aging and Sex on Corneal Nerve Density and Function.

Corneal nerves are instrumental in detecting mechanical, thermal, and chemical stimuli. They also contribute to the maintenance of corneal transparency by providing trophic support, regulating tear secretion, and initiating the blink reflex.¹ In addition to their well-known sensory and trophic activities, corneal nerves regulate the immune response by modulating leukocyte diapedesis and activation following infections and injuries.^2–4 Complete denervation is clinically epitomized by the development of neurotrophic keratitis. However, milder and/or partial nerve dysfunction can be found in most ocular surface diseases, including highly prevalent disorders such as dry eye disease (DED) and ocular neuropathic pain. Aging is a notable risk factor for many of these corneal disorders,^5,6 and, in fact, corneal nerve density, morphology, and function are significantly affected by aging. For example, it is known that the sub-basal nerve density decreases together with mechanical, chemical, and thermal sensitivity in older subjects.^7–11 These morphological and functional changes could be the consequence of altered corneal nerve expression of certain neuropeptides and neurotransmitters, including reductions in the levels of substance P (SP) and calcitonin gene-related peptide (CGRP).^9,12 Aging appears to affect not only the density of peripheral corneal fibers but also trigeminal neurons, where corneal nerves are generated, as it has been reported that transient receptor potential melastatin 8 (TRPM8)-positive trigeminal neurons undergo morphological and functional changes in aging animal corneas.¹³ It should be noted, however, that it is not known if and how aging has a different impact on corneal nerve morphology and/or function in males as opposed to females. This has relevant clinical implications because, for example, DED has a higher prevalence in female subjects,¹⁴ who are also more susceptible to nociceptive pain.¹⁵ Finally, limited knowledge is available on the potential cellular and molecular mechanisms underlying sex-based differences in corneal nerves during aging.