Sex, blinking, and dry eye

Abstract

Blinking sustains the corneal tear film generated by sexually dimorphic lacrimal and meibomian glands. Our study examines whether trigeminal control of blinking is also sexually dimorphic by investigating trigeminal reflex blinking, associative blink modification, and spontaneous blinking in male and female rats before and after unilateral dry eye caused by exorbital gland removal. Before gland removal, female rats exhibited a lower threshold for evoking trigeminal reflex blinks, a weaker effect of associative blink modification, and longer-duration spontaneous blinks than males. Spontaneous blink rate, reflex blink excitability, and occurrence of blink oscillations did not differ between the sexes. Reanalysis of previous data showed that humans showed the same blink sexual dimorphisms as rats. During the first 2 wk of dry eye, trigeminal blink circuit excitability and blink oscillations steadily rose in male rats, whereas excitability and blink oscillations did not change in females. Following dry eye, spontaneous blink duration increased for both males and females, whereas spontaneous blink rate remained constant for males but decreased for females. The associative modification treatment to depress trigeminal blink amplitude initially produced blink depression in males that converted to blink potentiation as trigeminal excitability rose, whereas females exhibited progressively more blink depression. These data indicated that dry eye increased excitability in male trigeminal reflex blink circuits at the expense of circuit modifiability, whereas trigeminal modifiability increased in females. This increased modifiability of female trigeminal blink circuits with dry eye may contribute to the preponderance of females developing the focal dystonia, benign essential blepharospasm. NEW & NOTEWORTHY All the elements controlling the corneal tear film are sexually dimorphic. Blinking, which smooths and maintains the tear film, also exhibits sex differences. Dry eye increases the sexual dimorphisms of blinking, including increased exaggeration of excitability in males and enhanced modifiability of the female trigeminal complex. This increased modifiability may explain female predominance in the development of the focal dystonia, benign essential blepharospasm.

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

“…Second, adequate testing of cold thermoreceptors and polymodal nociceptors requires isolated electrophysiological measurements of single corneal fibers in the excised mouse eyes, which was incompatible with our experimental design [ 63 ]. Third, alternative methods such as quantification of blinking rates or nocifensive behavior in response to diverse agonists do not necessarily provide direct evidence of corneal neuropathy because the readouts are conditioned by numerous factors: the non-linear effect of axonal damage on fiber excitability [ 64 – 66 ], the influence of the environment and sex [ 67 , 68 ], and the development of sensory crosstalk between cold thermoreceptors and polymodal nociceptors in the context of ocular surface inflammation [ 66 ]. In terms of nerve morphology, we analyzed the intraepithelial fibers at different levels (subapical, mid-epithelial, and subbasal) as they are the most affected segment of the corneal innervation in ocular surface disorders [ 5 , 6 ].…”

Shih-Tzu dogs show alterations in ocular surface homeostasis despite adequate aqueous tear production

“…Unlike reflex and voluntary blinking, spontaneous blinking is rapid, automatic and unconscious, with complete closure and opening of the eyelids [ 33 , 34 ]. In order for the tear film to spread over the entire ocular surface, there must be adequate tear production/secretion, as well as appropriate spreading and drainage, to maintain the physiological balance of the cornea [ 28 , 35 ]. In our study, the dogs evaluated had a high number of incomplete blinks and a low number of complete blinks.…”