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Yashar Seyed-Razavi, Laura Rincon Frutos, Carolina Luna García, Almudena Inigo-Portugues, M Carmen Acosta, Carlos Belmonte, Juana Gallar, Pedram Hamrah; Role of Resident Dendritic Cells on Corneal Cold Thermoreceptor Function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3309. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The intimate association between resident immune cells and corneal sensory nerve endings has been demonstrated. The purpose of this study was to determine whether corneal dendritic cells (DCs) influence spontaneous and stimulus-evoked activity of corneal cold sensory nerves.
Corneal DCs were depleted bilaterally in anaesthetized C57BL/6 CD11c-DTR mice (both sexes, 4-6 months old) by subconjunctival injections of diphtheria toxin (DT). The effect of short-term (2 days) and long-term (8 days) resident DC depletion on corneal nerve terminal impulse (NTI) activity from mice undergoing either one or numerous (4) rounds of depletion, respectively, was determined via a glass micropipette applied to the corneal surface of enucleated eyes in a recording chamber superfused with 34°C buffered saline solution (basal temperature). Ongoing NTI activity at basal temperature, response to cooling (decrease to 20°C), heating (increase to 45°C), as well as mechanical stimulation was recorded and analyzed off-line with Spike2 software. Age-matched C57BL/6 wild-type (WT) mice undergoing DT injection (sham depletion), naïve WT and CD11c-DTR mice served as controls. Data is presented as Mean±S.E.M. and significance determined by t-test or one-way ANOVA with Tukey post-hoc.
NTI results did not differ between naïve CD11c-DTR and naïve WT C57BL/6 control mice. NTI from sham- and short-term DC-depleted corneas revealed irregular firing activity, no significant changes in ongoing NTI activity, and slight elevations in cooling threshold (temperature (°C) during a cooling ramp at which NTI frequency in imp/sec increases greater than the mean basal frequency) (sham: 32.83±0.25 & short-term: 32.45±0.39 vs. 32.3±0.27°C, p=0.72 & 0.99, respectively) and peak frequency to cooling (NTI frequency (Hz) during cooling ramp) (33.46±7.00 & 42.60±7.96 vs. 27.88±4.07Hz, p=0.88 & 0.18, respectively), compared to naïve CD11c-DTR mice. Interestingly, analysis of long-term DC-depleted corneas revealed significant differences in cooling threshold (30.65±0.48°C vs. sham & naïve, p<0.01) and temperature at peak frequency (27.48±0.45 vs. sham: 31.64±0.49°C, p<0.001 & naïve CD11c-DTR: 29.89±0.42°C, p<0.01).
Our results demonstrate that long-term DC depletion results in significant changes in cold thermoreceptor activity. Our data suggests that resident DCs may be involved in regulating the function of cold nerve terminals in the cornea.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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