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Deshea Harris, Takefumi Yamaguchi, Aslihan Turhan, Ulrich von Andrian, Pedram Hamrah; Bilateral Up-regulation of Limbal Intravascular Adhesion Molecules Mediates Cell Infiltration into the Cornea after Unilateral Trigeminal Nerve Axotomy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2071.
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We have recently demonstrated that P-selectin and MAdCAM-1 mediate the recruitment of corneal dendritic cells after inflammation. Further, our group has demonstrated increased density of leukocytes in unaffected contralateral eyes in unilateral corneal diseases. The purpose of this study was to determine the neural involvement of the trigeminal nerve in up-regulation of these adhesion molecules.
Six- to 8-week-old adult BALB/c mice underwent trigeminal axotomy to transect the ophthalmic branch of the trigeminal nerve. Normal, axotomized, contralateral and sutured-induced inflamed corneas (n=3/group) were excised on post-operative days 3 and 7. RNA was isolated, DNAse treated, and converted to cDNA. Real-time PCR was performed using primers against the integrin MAdCAM-1 and P-selectin. Beta-actin and GAPDH were used as housekeeping genes and results were compared to normal and sutured controls. Homing of DC to the cornea was studied by immunostaining and confocal microscopy.
Following trigeminal axotomy, MAdCAM-1 was up-regulated both on post-operative day 3 (1.8-fold) and day 7 (1.6-fold). P-selectin was also up-regulated at day y (1.6-fold) and day 7 (1.9-fold) after axotomy. Interestingly, both MAdCAM-1 and P-selectin expression were even higher in contralateral unaffected corneas at day 3 (2.5-fold) and day 7 (2.8-fold) for MadCAM-1, and 1.8-fold for day 3) and 2.3-fold for day 7 for P-selectin, as compared to normal controls. The density of CD45+ cells in the center of the cornea significantly increased from 189+/-21 /mm2 to 550 +/-134 at day 3 and 979+/-45 at day 7 in the axotomized eye (P = 0.0015) and slightly increase to 247+/-25 at day 3 and 245+/-35 at day 7 in the contralateral eye (P = 0.595).
Our work demonstrates changes in the contralateral unaffected eyes as a response to ipsilateral trigeminal axotomy in mice. Trigeminal axotomy results in up regulation of the integrin MAdCAM-1 and P-selectin in both axotomized and in contralateral corneas, and suggest a neural regulation of limbal intravascular adhesion molecules.
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