Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
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The Role of nerve Growth Factor on Corneal Wound Healing in Dogs

  • 우흥명 (위스콘신대학교 수의과대학 외과학교실)
  • Published : 2001.12.01
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Abstract

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.

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.

Keywords

References

  1. Prog Growth Factor Res v.2 The nerve growth factor family Barde YA
  2. Invest Ophthalmol Vis Sci:inpress Morphology and immunohistochemistry of chronoc, non-septic, corneal epithelial defects in dogs Bentley E;Abram G;Reid TW;Cook C;Fisher C;Covitz D;Stur C;Hacker D;Murphy CJ
  3. Invest Ophthalmol Vis Sci v.42 The effect of repeated corneal epithelial and stormal morphology in the dog Bentley E;Campbell SF;Woo HM;Murphy CJ
  4. Proc Natl Acad Sci U S A v.64 The nerve growth factor: purification as a 30,000-molecular-weight protein Bocchini V;Angeletti PU
  5. Annu Rev Biochem v.47 Nerve growth factor Bradshaw RA
  6. Invest Ophthalmol Vis Sci v.41 The effect of growth factors, neuropeptides and neurotransmitters on NGF content in SV-40 transformed human corneal epithelial cells Campbell SF;Reid TW;Murphy CJ
  7. Endocrinology v.142 Nerve growth factor is required for early follicular development in the mammalian ovary Dissen GA;Romero C;Hirshfield AN;Ojeda SR
  8. Neuroscience v.49 Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo Donnercr J;Schuligoi R;Stein C
  9. Ontogenez v.30 The effect of in-situ nerve growth factor from different biological sources on the reinitiation of mouse oocyte meiotic maturation in culture and on parthenogenetic activation Fedorushchenko AN;Koval TI;Khamidov DK
  10. Exp Eye Res v.66 Peptidergic innervation of the rat cornea Jones MA;Marfurt CF
  11. Cell v.65 The trk proto-oncogene encodes a receptor for nerve growth factor Klein R;Jing SQ;Nanduri V;O'Rourke E;Barbacid M
  12. Invest Ophthalmol Vis Sci v.34 Growth factors modulate clonal growth and differentiation of cultured rabbit limbal and corneal epithelium Kruse FE;Tseng SC
  13. Arch Ophthalmol v.118 Anti-inflammatory and healing properties of nerve growth factor in immune corneal ulcers with stromal melting Lambiase A;Bonini S;Aloe L;Rama P
  14. Invest. Ophthalmol. Vis. Sci v.41 Nerve Growth Factor Promotes Corneal Healing: Structural, Biochemical, and Molecular Analyses of Rat and Human Corneas Lambiase A;Manni L;Bonini S;Rama P;Micera A;Aloe L
  15. N Engl J Med v.338 Topical treatment with nerve growth factor for corneal neurotrophic ulcers Lambiase A;Rama P;Bonini S;Caprioglio G;Aloe L
  16. Invest Ophthalmol Vis Sci v.37 Migration and proliferation characteristics of SV-40 transformed human corneal epithelial cells in response to neuropeptides (ARVO abstract) Lee CH;Nelson M;Barney NP;Brightbill FS;Araki-Sasaki K;Reid TW;Murphy CJ
  17. J Neurosci Res v.8 Failure of nerve growth factor to enhance wound healing in the hamster Leitzel K;Cano C;Marks J, Jr.;Lipton A
  18. Proc Natl Acad Sci U S A v.77 Nerve growth factor: acceleration of the rate of wound healing in mice Li AK;Koroly MJ;Schattenkerk ME;Malt RA;Young M
  19. J Comp Neurol v.336 Immunohistochemical localization of tyrosine hydroxylase in corneal nerves Marfurt CF;Ellis LC
  20. J Exp Med v.187 Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice Matsuda H;Koyama H;Sato H;Sawada J;Itakura A;Tanaka A;Matsumoto M;Konno K;Ushio H;Matsuda K
  21. Invest Ophthalmol Vis Sci v.41 Modulation of SV-40 transformed human corneal epithelial cell proliferation, migration, and adhesion by nerve growth factor (ARVO abstract) Murphy CJ;Campbell SF;Reid TW
  22. Invest Ophthalmol Vis Sci:in press Chronic non-septiccorneal ephithelial fefects in dogs: Clinical fetures, innervation and effect of topical SP and IGF-1 Murphy CJ;Marfurt CF;MaDermott C;Bentley E;Abram G;Reid TW;Campbell S
  23. Neurisci Res v.35 Nerve growth factor stimulates synthesis of calcitonin gene-related peptide in dorsal root ganglion cells during sensory regeneration in capsaicin-treated rats Schicho R;Donnerer J
  24. Proc Natl Acad Sci U S A v.81 Expression of the beta-nerve growth factor gene corrclates with the density of sympathetic innervation in effector organs Shelton DL;Reichardt LF
  25. Annu Rev Neurosci v.24 Early days of the nerve growth factor proteins Shooter EM
  26. Cell v.77 Functions of the neurotrophins during nervous system development: what the knockouts are teaching us Snider WD
  27. Mol Biol Rep v.23 Regulation and clinical implications of corneal epithelial stem cells Tseng SC
  28. Invest Ophthalmol Vis Sci v.41 Effects of oleoresin capsicum pepper spray on human corneal morphology and sensitivity Vesaluoma M;Muller L;Gallar J;Lambiase A;Moilanen J;Hack T;Belmonte C;Tervo T
  29. J Exp Med v.191 Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system Villoslada P;Hauser SL;Bartke I;Unger J;Heald N;Rosenberg D;Cheung SW:Mobley WC;Fisher S;Genain CP
  30. Br J Ophthalmol v.85 Effects of amniotic membrane on epithelial wound healing and stromal remodeling after excimer laser keratectomy in rabbit cornea Woo HM;Kim MS;Kweon OK;Kim DY;Nam TC;Kim JH
  31. Biochemistry v.17 Nerve growth factor: multiple dissociation products in homogenates of the mouse submandibular gland. Purification and molecular properties of the intact undissociated form of the protein Young M;Saide JD;Murphy RA;Blanchard
  32. J neurosci Res v.46 Detection of increased tissue concentrations of nerve growth factor with an improved extraction procedure Zettler C;Bridges DC;Zhou XF;Rush RA