Please use this identifier to cite or link to this item:
標題: 評估豬小腸黏膜下基質與結膜瓣對兔角膜深層潰瘍之影響
A Comparative Study of Using Porcine Small Intestinal Submucosa and Conjunctival Flap for Repairing Deep Corneal Ulcer in Rabbit Model
作者: 劉凱昀
Kai-Yun Liu
關鍵字: 結膜瓣
conjunctival flap
small intestinal submucosa
corneal ulcer
引用: Aiken S, Badylak S, Toombs J, Shelbourne K, Hiles M, Lantz G, Van Sickle D. Small intestinal submucosa as an intra-articular ligamentous graft material: a pilot study in dogs. VCOT Archive 7(3):36-40, 1994. Ambati BK, Joussen AM, Ambati J, Moromizato Y, Guha C, Javaherian K, Gillies S, O'reilly MS, Adamis AP. Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 120(8):1063-1068, 2002. Andia I, Abate M. Platelet-rich plasma: underlying biology and clinical correlates. Regenerative medicine 8(5):645-658, 2013. Arima T, Uchiyama M, Nakano Y, Nagasaka S, Kang D, Shimizu A, Takahashi H. Peroxisome proliferator-activated receptor alpha agonist suppresses neovascularization by reducing both vascular endothelial growth factor and angiopoietin-2 in corneal alkali burn. Sci Rep 7(1):17763, 2017. Assaad NN, Chong R, Tat LT, Bennett MH, Coroneo MT. Use of adjuvant hyperbaric oxygen therapy to support limbal conjunctival graft in the management of recurrent pterygium. Cornea 30(1):7-10, 2011. Azar DT. Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing. Trans Am Ophthalmol Soc 104:264-302, 2006. Badylak SF. Small intestinal submucosa (SIS): a biomaterial conducive to smart tissue remodeling. Tissue engineering Springer:179-189, 1993. Badylak SF. The extracellular matrix as a scaffold for tissue reconstruction. Semin Cell Dev Biol (5):377-83, 2002. Badylak SF, Coffey AC, Lantz GC, Tacker WA, Geddes LA. Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model. J Vasc Surg 19(3):465-472, 1994. Badylak SF, Tullius R, Kokini K, Shelbourne KD, Klootwyk T, Voytik SL, Kraine MR, Simmons C. The use of xenogeneic small intestinal submucosa as a biomaterial for Achille's tendon repair in a dog model. J Biomed Mater Res (8):977-985, 1995. Balland O, Poinsard AS, Famose F, Goulle F, Isard PF, Mathieson I, Dulaurent T. Use of a porcine urinary bladder acellular matrix for corneal reconstruction in dogs and cats. Vet Ophthalmol 19(6):454-463, 2016. Barros PS, Safatle A, Godoy CA, Souza MS, Barros LF, Brooks DE. Amniotic membrane transplantation for the reconstruction of the ocular surface in three cases. Vet Ophthalmol 8(3):189-192, 2005. Baum J. Amniotic membrane transplantation: why is it effective? Cornea 21(4):339-341, 2002. Bito LZ. Species differences in the responses of the eye to irritation and trauma: a hypothesis of divergence in ocular defense mechanisms, and the choice of experimental animals for eye research. Exp Eye Res 39(6):807-829, 1984. Bourne WM, Nelson LR, Hodge DO. Central corneal endothelial cell changes over a ten-year period. Invest Ophthalmol Vis Sci 38(3):779-782, 1997. Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res 163(4):268-285, 2014. Bussieres M, Krohne SG, Stiles J, Townsend WM. The use of porcine small intestinal submucosa for the repair of full‐thickness corneal defects in dogs, cats and horses. Vet Ophthalmol 7(5):352-359, 2004. Chen SC, Telinius N, Lin HT, Huang MC, Lin CC, Chou CH, Hjortdal J. Use of fish scale-derived BioCornea to seal full-thickness corneal perforations in pig models. PloS one 10(11):e0143511, 2015. Chow DW, Westermeyer HD. Retrospective evaluation of corneal reconstruction using ACell Vet™ alone in dogs and cats: 82 cases. Vet Ophthalmol 19(5):357-366, 2016. Clarke KM, Lantz GC, Salisbury SK, Badylak SF, Hiles MC, Voytik SL. Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs. J Surg Res 60(1):107-114, 1996. Cook JL, Tomlinson JL, Kreeger JM, Cook CR. Induction of meniscal regeneration in dogs using a novel biomaterial. Am J Sports Med 27(5):658-665, 1999. Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, Bouck NP. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285(5425):245-248, 1999. Dejardin LM, Arnoczky SP, Clarke RB. Use of small intestinal submucosal implants for regeneration of large fascial defects: an experimental study in dogs. J Biomed Mater Res 46(2):203-211, 1999. DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg 37(3):588-598, 2011. Dorbandt DM, Moore PA, Myrna KE. Outcome of conjunctival flap repair for corneal defects with and without an acellular submucosa implant in 73 canine eyes. Vet Ophthalmol 18(2):116-122, 2015. Edwards DR, Murphy G, Reynolds J, Whitham S, Docherty A, Angel P, Heath J. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J 6(7):1899-1904,1987. Featherstone HJ, Sansom J, Heinrich CL. The use of porcine small intestinal submucosa in ten cases of feline corneal disease. Vet Ophthalmol 4(2):147-153, 2001. Fini ME, Cook JR, Mohan R. Proteolytic mechanisms in corneal ulceration and repair. Arch Dermatol Res 290(1):S12-23, 1998. Gabison EE, Huet E, Baudouin C, Menashi S. Direct epithelial-stromal interaction in corneal wound healing: Role of EMMPRIN/CD147 in MMPs induction and beyond. Prog Retin Eye Res 28(1):19-33, 2009. Gabison EE, Mourah S, Steinfels E, Yan L, Hoang-Xuan T, Watsky MA, De Wever B, Calvo F, Mauviel A, Menashi S. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction. Am J Pathol 166(1):209-219, 2005. Gelatt KN, Gelatt JP. Surgical procedures for the conjunctiva and the nictitating membrane. In: Gelatt KN, Brooks DE, ed. Veterinary Ophthalmic Surgery. 1^st. Elsevier Health Sciences, 157-190, 2011. Gelatt KN, Gilger BC, Kern TJ. Conjunctiva. In: Maggs DJ, ed. Veterinary ophthalmology. 5^th. John Wiley & Sons, 140-158, 2012. Gilbert TW, Stewart-Akers AM, Simmons-Byrd A, Badylak SF. Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair. J Bone Joint Surg Am 89(3):621-630, 2007. Goulle F. Use of porcine small intestinal submucosa for corneal reconstruction in dogs and cats: 106 cases. J Small Anim Pract 53(1):34-43, 2012. Griguer F, Raymond I, Regnier A. Preliminary evaluation of the biocompatibility of the small intestinal submucosa (SIS) biomaterial with the rabbit cornea. Revue Med Vet 152(8-9):597-604, 2001. Gwin RM, Warren JK, Samuelson DA, Gum GG. Effects of phacoemulsification and extracapsular lens removal on corneal thickness and endothelial cell density in the dog. Invest Ophthalmol Vis Sci 24(2):227-236, 1983. Hacker D. Frozen corneal grafts in dogs and cats: a report on 19 cases. J Am Anim Hosp Assoc, USA, 1991. Hakanson N, Lorimer D, Merideth R. Further comments on conjuctival pedicle grafting in the treatment of corneal ulcers in the dog and cat. J Am Anim Hosp Assoc, USA, 1988. Hakanson N, Merideth R. Conjunctival pedicle grafting in the treatment of corneal ulcers in the dog and cat. J Am Anim Hosp Assoc, USA, 1987. Hansen PA, Guandalini A. A retrospective study of 30 cases of frozen lamellar corneal graft in dogs and cats. Vet Ophthalmol 2(4):233-241, 1999. Hobden JA, Rootman DS, O'Callaghan RJ, Hill JM. Iontophoretic application of tobramycin to uninfected and Pseudomonas aeruginosa-infected rabbit corneas. Antimicrob Agents Chemother 32(7):978-981, 1988. Hodde JP, Badylak SF, Brightman AO, Voytik-Harbin SL. Glycosaminoglycan content of small intestinal submucosa: a bioscaffold for tissue replacement. Tissue Eng 2(3):209-217, 1996. Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261(9):4337-4345, 1986. Keene DR, Sakai LY, Lunstrum GP, Morris NP, Burgeson RE. Type VII collagen forms an extended network of anchoring fibrils. J Cell Biol 104(3):611-621, 1987. Kim JY, Won H-J, Jeong S. A retrospective study of ulcerative keratitis in 32 dogs. Intern J Appl Res Vet Med 7(1):27-31, 2009. Klenkler B, Sheardown H. Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology. Exp Eye Res 79(5):677-688, 2004. Klyce S. Stromal lactate accumulation can account for corneal oedema osmotically following epithelial hypoxia in the rabbit. J Physiol 321(1):49-64, 1981. Kropp BP, Rippy MK, Badylak SF, Adams MC, Keating MA, Rink RC, Thor KB. Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologic assessment in long-term canine bladder augmentations. J Urol 155(6):2098-2104, 1996. Lassaline ME, Brooks DE, Ollivier FJ, Komaromy AM, Kallberg ME, Gelatt KN. Equine amniotic membrane transplantation for corneal ulceration and keratomalacia in three horses. Vet Ophthalmol 8(5):311-317, 2005. Latendresse JR, Warbrittion AR, Jonassen H, Creasy DM. Fixation of testes and eyes using a modified Davidson's fluid: comparison with Bouin's fluid and conventional Davidson's fluid. Toxicol Pathol 30(4):524-533, 2002. Leung DW, Cachianes G, Kuang W-J, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306-1309, 1989. Lewin G. Repair of a full thickness corneoscleral defect in a German shepherd dog using porcine small intestinal submucosa. J Small Anim Pract 40(7):340-342, 1999. Li W, Grayson G, Folkman J, D'Amore PA. Sustained-release endotoxin. A model for inducing corneal neovascularization. Invest Ophthalmol Vis Sci 32(11):2906-2911, 1991. Li ZN, Yuan ZF, Mu GY, Hu M, Cao LJ, Zhang YL, Liu L, Ge MX. Inhibitory effect of polysulfated heparin endostatin on alkali burn induced corneal neovascularization in rabbits. Int J Ophthalmol 8(2):234, 2015. Lim LS, How AC, Ang LP, Tan DT. Gundersen flaps in the management of ocular surface disease in an Asian population. Cornea 28(7):747-751, 2009. Lin HF, Lai YC, Tai CF, Tsai JL, Hsu HC, Hsu RF, Lu SN, Feng NH, Chai CY, Lee CH. Effects of cultured human adipose-derived stem cells transplantation on rabbit cornea regeneration after alkaline chemical burn. Kaohsiung J Med Sci 29(1):14-18, 2013. Lin MT, Chen Y. Effect of copper ion on collagenase release. Its implication in corneal vascularization. Invest Ophthalmol Vis Sci 33(3):558-563, 1992. Maggs DJ, Miller P, Ofri R. Conjunctiva. In: Maggs DJ, ed. Slatter's fundamentals of veterinary ophthalmology. 5^th.Elsevier Health Sciences, 140-158, 2012 Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res 90(4):478-492, 2010. Matsuda M, Ubels J, Edelhauser H. A larger corneal epithelial wound closes at a faster rate. Invest Ophthalmol Vis Sci 26(6):897-900, 1985. McPherson TB, Badylak SF. Characterization of fibronectin derived from porcine small intestinal submucosa. Tissue Eng 4(1):75-83, 1998. Meek KM, Knupp C. Corneal structure and transparency. Prog Retin Eye Res 49:1-16, 2015. Meinert M, Eriksen GV, Petersen AC, Helmig RB, Laurent C, Uldbjerg N, Malmström A. Proteoglycans and hyaluronan in human fetal membranes. Am J Obstet Gynecol 184(4):679-685, 2001. Melles GR, Binder PS, Anderson JA. Variation in healing throughout the depth of long-term, unsutured, corneal wounds in human autopsy specimens and monkeys. Archives of Ophthalmology 112(1):100-109, 1994. Mishima S. 1965. Some physiological aspects of the precorneal tear film. Arch Ophthalmol 73(2):233-241. Miyazono K. Regulation of Transforming Growth Factor‐β Signaling and Vascular Diseases. Cornea 21:S48-S53, 2002. Modesti A, Scarpa S, D'Orazi G, Simonelli L, Caramia FG. Localization of type IV and V collagens in the stroma of human amnion. Prog Clin Biol Res 296:459-463, 1989. Morgan PB, Maldonado-Codina C. Corneal staining: do we really understand what we are seeing? Cont Lens Anterior Eye 32(2):48-54, 2009. Munger RJ. Veterinary ophthalmology in laboratory animal studies. Vet Ophthalmol 5(3):167-175, 2002. Nakamura M, Sato N, Chikama T, Hasegawa Y, NishidaT. Fibronectin facilitates corneal epithelial wound healing in diabetic rats. Exp Eye Res 64(3):355-359, 1997. Ollivier FJ. Bacterial corneal diseases in dogs and cats. Clin Tech Small Anim Pract 18(3):193-198, 2003. Park WC, Tseng SC. Modulation of acute inflammation and keratocyte death by suturing, blood, and amniotic membrane in PRK. Invest Ophthalmol Vis Sci 41(10):2906-2914, 2000. Prado MR, Rocha MF, Brito ÉH, Girão MD, Monteiro AJ, Teixeira MF, Sidrim JJ. Survey of bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Fortaleza, Ceará, Brazil. Vet Ophthalmol 8(1):33-37,2005. Robers A. Transforming growth factor-beta. Major role in regulation of extracellular matrix. Ann NY Acad Sci 580:225-232, 1990. Schultz G, Chegini N, Grant M, Khaw P, MacKay S. Effects of growth factors on corneal wound healing. Acta Ophthalmol Suppl 70(202):60-66, 1992. Shapiro M, Friend J, Thoft R. Corneal re-epithelialization from the conjunctiva. Invest Ophthalmol Vis Sci 21(1):135-142, 1981. Shariati A, Ameri H, Hinton D, Humayun M. The Effects of Davidson's Fixative Solution in Preserving the Rabbit Eye. Invest Ophthalmol Vis Sci 49(13):5207, 2008. Soontornvipart K, Tuntivanich N, Kecova H, Raušer P. Conjunctival pedicle graft in dogs and cats: a retrospective study of 88 cases. Acta Vet Brno 72(1):63-69, 2003. Strissel KJ, Rinehart WB, Fini ME. A corneal epithelial inhibitor of stromal cell collagenase synthesis identified as TGF-beta 2. Invest Ophthalmol Vis Sci 36(1):151-162, 1995. Tolar EL, Hendrix DV, Rohrbach BW, Plummer CE, Brooks DE, Gelatt KN. Evaluation of clinical characteristics and bacterial isolates in dogs with bacterial keratitis: 97 cases (1993–2003). J Am Vet Med Assoc 228(1):80-85, 2006. Tseng SC, Li DQ, Ma X. Suppression of transforming growth factor‐beta isoforms, TGF‐β receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol 179(3):325-335, 1999. Vanore M, Chahory S, Payen G, Clerc B. Surgical repair of deep melting ulcers with porcine small intestinal submucosa (SIS) graft in dogs and cats. Vet Ophthalmol 10(2):93-99, 2007. Voytik‐Harbin SL, Brightman AO, Kraine MR, Waisner B, Badylak SF. Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 67(4):478-491, 1997. Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-β. Immunol today 10(8):258-261, 1989. Wang L, Pan Q, Xue Q, Cui J, Qi C. Evaluation of matrix metalloproteinase concentrations in precorneal tear film from dogs with Pseudomonas aeruginosa-associated keratitis. Am J Vet Res 69(10):1341-1345, 2008. Wang L, Pan Q, Zhang L, Xue Q, Cui J, Qi C. Investigation of bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Beijing, China. Vet Ophthalmol 11(3):145-149, 2008. Wang SB, Hu KM, Seamon KJ, Mani V, Chen Y, Gronert K. Estrogen negatively regulates epithelial wound healing and protective lipid mediator circuits in the cornea. FASEB J 26(4):1506-1516, 2012. Weir AB, and Collins M. Toxicologic Pathology of the Eye: Histologic Preparation and Alterations of the Anterior Segment. In Kenneth AS, James AR ed. Assessing ocular toxicology in laboratory animals. Springer Science and Business Media, Lodon, 159-217, 2012. Wentworth JS, Paterson CA, Wells JT, Tilki N, Gray RS, McCartney MD. Collagen shields exacerbate ulceration of alkali-burned rabbit corneas. Arch Ophthalmol 111(3):389-389, 1993. Wiley L, SundarRaj N, Sun T, Thoft R. Regional heterogeneity in human corneal and limbal epithelia: an immunohistochemical evaluation. Invest Ophthalmol Vis Sci 32(3):594-602, 1991. Wilkie DA, Whittaker C. Surgery of the cornea. Vet Clin North Am Small Anim Pract 27(5):1067-1107, 1997. Wilson SE, Chaurasia SS, Medeiros FW. Apoptosis in the initiation, modulation and termination of the corneal wound healing response. Exp Eye Res 85(3):305-311, 2007. Wu Z, Zhou Y, Li N, Huang M, Duan H, Ge J, Xiang P, Wang Z. The use of phospholipase A2 to prepare acellular porcine corneal stroma as a tissue engineering scaffold. Biomaterials 30(21):3513-3522, 2009. Zhang Q, Yan B, Zhou H, Wang C. Alteration in bulbar conjunctiva microcirculation and interventional effect of Pentoxifylline after high-voltage electrical burn in rabbits. Zhonghua Shao Shang Za Zhi 26(3):185-191, 2010. Zhou Q, Long X, Zhu X. Improved conjunctival transplantation for corneal ulcer. Zhong Nan Da Xue Xue Bao Yi Xue Ban 35(8):814-818, 2010. Zhou Y, Wu Z, Ge J, Wan P, Li N, Xiang P, Gao Q, Wang Z. Development and characterization of acellular porcine corneal matrix using sodium dodecylsulfate. Cornea 30(1):73-82, 2011
摘要: 角膜潰瘍是小動物非常常見的眼科疾病之一,嚴重的角膜潰瘍或穿孔可能會影響到眼球的完整性或導致失明,故常常需要手術的介入治療。傳統的手術治療方式以結膜瓣最為常見,近幾年也有其他生物材質正在被研發,以治療嚴重的角膜問題,其中豬小腸黏膜下基質(porcine small intestinal submucosa;SIS) 是臨床最常被使用的材質之一。然而,在一篇研究中卻顯示以結膜瓣單獨治療角膜深層潰瘍或穿孔的成功率,與以結膜瓣合併SIS治療的成功率無統計上的顯著差異(Dorbandt et al. 2015)。本實驗欲研究以兔子模式下使用結膜瓣、SIS及結膜瓣合併SIS對於角膜深層潰瘍之治療效果比較。 實驗對象為36隻紐西蘭白兔(72隻眼睛),依照不同的治療方式分為結膜瓣、SIS與結膜瓣合併SIS三大組,每大組再依據犧牲時間分為:術後一週、術後兩週、術後三週、術後四週,四小組。每隻實驗兔先以人為的方式於其角膜製造深層角膜潰瘍,再分別以結膜瓣、SIS及結膜瓣合併SIS治療。術後第一週每天檢查一次,第二週後每週檢查一次,檢查項目包括臨床症狀與角膜缺損大小。當實驗結束後實驗兔的角膜會被取下製作組織病理切片。檢查結果SIS與結膜瓣組,以及SIS與結膜瓣合併SIS組的臨床症狀分數皆於術後第2、4、5、6天具有統計上的顯著差異,然而在第28天時三組之間臨床症狀分數皆無統計上的顯著差異。組織病理學檢查顯示角膜有輕微至嚴重的多核白血球與巨噬細胞的浸潤。本實驗結果顯示單獨使用結膜瓣或SIS與結膜瓣合併SIS對於角膜深層潰瘍的治療,對於角膜上皮癒合或改善臨床症狀皆無統計學上的顯著差異。
Corneal ulceration is a common ocular injury in small animals. A severe corneal defect or perforation may progress to threaten globe integrity and vision. The surgical procedure most commonly used for deep corneal ulcers is a conjunctival flap or graft. In recent years, the use of small intestinal submucosa (SIS) is one of the newer grafting methods used to surgically manage severe corneal disorders. However, there is no significant difference in success rate between using conjunctival flap alone and using conjunctival flap in addition to SIS (Dorbandt et al. 2015). The purpose of this study is to compare the efficiency of SIS, conjunctival flap and SIS with conjunctival flap for repairing deep corneal ulcer in rabbit model. Thirty-six New Zealand rabbits (72 eyes) were used in this study and divided into three groups. Every groups were divided into four small groups: 1week post-injury, 2 weeks post-injury, 3 weeks post-injury, and 4 weeks post-injury. All eyes were treated with conjunctival flap, SIS and conjunctival flap alone with SIS respectively after making artificial deep corneal ulcer. Clinical signs and corneal epithelial defect area were recorded every day for the first week, and recorded weekly after the first week. The corneas were excised for histopathological examination when the record was finished. There was statistically difference in the sum of clinical sign score between the SIS group and conjunctival flap alone with SIS group, and between the SIS group and conjunctival flap group 2, 4, 5, 6 days after injury. There was no statistically difference in the sum of clinical sign score among the groups 28 days after injury. Histopathological examination of the corneas showed mild to severe infiltration of polymorphonuclear leukocytes and macrophages. Treatment with pocrine small intestinal submucosa with and without conjunctival flap, and conjunctival flap alone for repairing deep corneal ulcer did not reveal the efficacy of accelerating corneal epithelial healing or improving clinical signs in this study.
文章公開時間: 2018-08-20
Appears in Collections:獸醫學系所



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.