EFFECTS OF TEAR DEFICIENCY ON CORNEAL NERVE MORPHOLOGY AND SENSORY NERVE ACTIVITY IN YOUNG AND ADULT GUINEA PIGS

Abstract

 

Purpose

 

To examine the effect of experimentally induced tear-deficiency (TD) on the morphology and impulse activity of corneal sensory nerve fibers in guinea pigs during maturation.

 

Methods

 

The morphological changes of corneal nerves were studied in different age groups (1-12 months, n=36) and 1, 3 and 8 months after the main lacrimal gland surgical ablation (n=34) performed in 1-month old animals. Eyes were processed for neuronal class III β-tubulin staining, analyzing the proportion of subbasal nerve fibers, the number, density and length of subbasal nerve leashes and the density of epithelial nerve terminals both in the whole mount cornea and in different zones of the superior quadrant. The activity of corneal sensory nerves was measured using electrophysiological extracellular recording techniques. Spontaneous and stimulus-evoked impulse activity were measured in 1 and 8 months animals after lacrimal gland removal and in their age-matched controls.

 

Results

 

In intact guinea pigs, the number and density of subbasal nerve leashes was different between 1-month and 12-months animals, with both parameters reaching their peak values at month 2 (1834 ± 135 nerves; 53,9 nerves/mm²). The increase in length of subbasal nerves was significantly correlated with age and with the growth of corneal surface area (P<0.001). The density of nerve terminals and nerve branches decreased with age. In operated animals, changes in corneal subbasal nerve architecture were observed 1 month after lacrimal gland removal (see table) but not at later periods. These data suggest that nerve damage develops shortly after induction of reduced tearing, which causes a transient decrease in the number and density of subbasal nerve leashes, as well as in the density of nerve fibers and terminals. After induction of tear-deficiency, significant changes in nerve impulse activity were found only in cold thermoreceptor nerve activity of the 2 months old animals in comparison with controls.

 

Conclusions

 

The post-natal corneal nerve architecture in guinea pigs changes during maturation to adulthood. Tear deficiency induces a reduction in the subbasal and epithelial nerve density that occurs in parallel with alterations in the activity of corneal cold sensory nerve fibers, suggesting that functional disturbances in nerve activity caused by eye dryness are primarily due to injury of corneal cold sensory nerve fibers.