Corneal sensory nerve activity in an experimental model of UV keratitis.
OBJECTIVE
To produce in guinea pigs a UV-induced keratitis, to analyze the effects of this pathology on corneal nerve activity.


METHODS
In anesthetized animals, one eye was exposed to 254 nm UV-C radiation (500-1000 mJ/cm(2)), excised 24 to 48 hours later and superfused in vitro. Nerve impulse activity was recorded in ciliary nerve filaments or in corneal sensory terminals of intact and UV-irradiated eyes. Impulse activity in response to mechanical (von Frey hairs), chemical (98.5% CO2 gas jets), and thermal stimulation (cooling from 34°C to 20°C; heating to 50°C) was analyzed. Duration of eyelid closure and blinking and tearing rates were evaluated in control and in UV-irradiated eyes, before and after application of TRPV1, TRPA1, and TRPM8 agonists (100 μM capsaicin; 10 mM AITC, and 200 μM menthol, respectively).


RESULTS
After irradiation, mechanical threshold of mechano-nociceptor corneo-scleral fibers was reduced (0.59 ± 0.4 vs. 0.27 ± 0.07 mN; P < 0.05) while polymodal nociceptors increased their response to chemical stimulation (1.7 ± 0.2 vs. 3.4 ± 0.5 imps/s; P < 0.05). In contrast, cold thermoreceptors showed a significantly lower ongoing activity at 34°C (8.6 ± 0.5 vs. 6.1 ± 0.9 imp/s; P < 0.05) and a reduced responsiveness to cooling pulses (peak frequency = 29.8 ± 1.3 vs. 18.9 ± 1.8 imp/s; P < 0.001). Blinking but not tearing rate was significantly higher; behavioral responses to topical capsaicin and AITC, but not to menthol were enhanced in UV-irradiated animals.


CONCLUSIONS
Sensitization of nociceptor and depression of cold thermoreceptor activity following UV radiation appear to result from an action of inflammatory mediators on TRP channels selectively expressed by sensory nerve terminals. Changes in nerve activity possibly underlie discomfort sensations associated with corneo-conjunctival inflammation induced by UV exposure.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain.
M Carmen
MC
Acosta
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain.
Carolina
C
Luna
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain.
Susana
S
Quirce
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain Fundación de Investigación Oftalmológica, Instituto Fernández-Vega, C/Drs. Fernández Vega, s/n, Oviedo, Spain.
Carlos
C
Belmonte
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain.
Juana
J
Gallar
D000818:Animals; D001767:Blinking; D003315:Cornea / Q000294:innervation* / Q000473:pathology / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D007634:Keratitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000502:physiology* / Q000528:radiation effects; D013823:Thermoreceptors / Q000503:physiopathology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
UV-induced inflammation; corneal innervation; photokeratitis