각막상피의 창상치유에 중요한 역할을 하는 것으로 알려진 Nerve Growth Factor(NGF)의 내인성 변화와 국소적 투여효과를 알아보았다. 6마리의 Beagle 을 사용하여 비교군인 오른쪽 눈에만 6mm의 기계적인 각막 창상을 만들었고 왼쪽 눈은 대조군으로 사용하였다. 눈물은 수술후 1주일동안 매일, 각막 상피는 수술중 그리고 수술후 7일에 각각 채취하여 NGF 농도를 enzyme-linked immunosorbent assay (ELISA)를 사용하여 측정하였다. 2차 실험으로, 16마리의 Bealgle을 사용하여 오른쪽 눈에 위와 동일한 창상을 만든 후, 창상 부위가 회복될 때까지 recombinant human (rh) NGF (n=4), murine NGF (n=6) 그리고 anti-NGF blocking antibody (n=6)를 6시간마다 점안하였으며, 왼쪽 눈은 bovine serum albumin (BSA)를 점안하여 대조군으로 사용하였다. 창상 면적은 NIH image software를 이용하여 분석하였다. 대조군에 비하여, 비교군의 눈물내 NGF는 치유초기에 현저하게 증가하였으며, 각막 상피의 NGF도 유의적인 증가를 보였다. 그러나 rh NGF, murine NGF, anti-NGF blocking antibody처치군과 BSA처치군 간에는 각막창상 치유에 유의적인 차이가 인정되지 않았다. 각막창상후, rh NGF 혹은 murine NGF의 추가적인 국소점안은 정상개의 각막상피 치유에 효과가 없었으나, 창상후 초기 치유기동안 눈물과 손상받은 각막상피에서 내인성 NGF의 급격한 보상성 증가로 미루어 NGF는 각막 상피의 창상치유에 중요한 역할을 하는 것으로 사료된다.
To investigate the modulation of nerve growth factor (NGF) during corneal epithelial wound healing and the effect of topical NGF on corneal epithelial wound healing in dogs. An axial epithelial defect was created in the right eye using 6mm axial corneal mechanical debridement while the left served as an unwounded control. The tears were collected from both eyes during 1 week and the corneal epithelium was processed for the measurement of NGF at day 0 and 7. The NGF content of tears and corneal epithelium was determined by enzyme-linked immunosorbent assay. In another experiment, the animals were divided into 3 groups. The right eyes in each group were treated every six hours with 200 ug/ml of recombinant human (rh) NGF, murine NGF, or 600 ug/ml of anti-NGF blocking antibody. The left eye of each animal was treated with bovine serum albumin (BSA) to serve as controls. Wound healing was analyzed using NIH image software. Tear NGF was markedly increased in the wounded eyes, relative to tears from control eyes during the early healing period. The NGF content of the corneal epithelium was elevated in the wounded eye (p=0.024). Time to wound closure and rate of epithelial migration were not significantly different between the NGF treated or the NGF antibody treated, and the control BSA treated eyes. Corneal epithelial wounding increased NGF content only on the wounded side during the early healing period. Neither topical recombinant human or murine NGF affected corneal epithelial wound healing in the normal dog.
