The pathogenesis of pterygium: Current concepts and their therapeutic implications

Ocular Surface

Volumn 6, Issue 1, 2008, Pages 24-43

  Chui, Jeanie ^a   di Girolamo, Nick ^a   Wakefield, Denis ^a   Coroneo, Minas T ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Corneal nerves; Epithelial mesenchymal transition; Genetics; Oxidative stress; Pathogenesis; Pterygium; Stem cells; UV light

Indexed keywords

ALPHA2A INTERFERON; ANGIOGENESIS INHIBITOR; ANTIFIBROTIC AGENT; BEVACIZUMAB; CALCITONIN GENE RELATED PEPTIDE; CYCLOSPORIN A; CYTOKINE; EPIDERMAL GROWTH FACTOR RECEPTOR; EVEROLIMUS; FLUOROURACIL; FUMAGILLIN; FUMAGILLOL CHLOROACETYLCARBAMATE; GLUTATHIONE TRANSFERASE M1; GROWTH FACTOR RECEPTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; MATRIX METALLOPROTEINASE; METHIONYL AMINOPEPTIDASE 2; MITOGEN ACTIVATED PROTEIN KINASE; MITOMYCIN C; PIGMENT EPITHELIUM DERIVED FACTOR; PIOGLITAZONE; PPI 2458; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RETINOIC ACID; STEROID; STRESS ACTIVATED PROTEIN KINASE; THIOTEPA; UNINDEXED DRUG; VASCULOTROPIN INHIBITOR;

ADJUVANT THERAPY; ALOPECIA; ANGIOGENESIS; CELL PROLIFERATION; CLINICAL TRIAL; CORNEA DISEASE; DISEASE ASSOCIATION; DNA FLANKING REGION; DNA REPAIR; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; DRY EYE; ELECTRON THERAPY; EPITHELIUM CELL; EXCISION; EXTRACELLULAR MATRIX; FIBROSIS; FLU LIKE SYNDROME; GENETIC ANALYSIS; HEMATOPOIETIC STEM CELL; HEREDITY; HETEROZYGOSITY LOSS; HUMAN; INFLAMMATORY INFILTRATE; LONG TERM EXPOSURE; MESENCHYME CELL; MICROSATELLITE INSTABILITY; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PHENOTYPE; PRECANCER; PROTEIN ANALYSIS; PROTEIN FUNCTION; PTERYGIUM; RADIATION EXPOSURE; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN CANCER; SURGICAL TECHNIQUE; ULTRAVIOLET RADIATION; UNSPECIFIED SIDE EFFECT; ANIMAL; EYE SURGERY; NEOVASCULARIZATION (PATHOLOGY); TREATMENT OUTCOME;

ANGIOGENESIS INHIBITORS; ANIMALS; HUMANS; NEOVASCULARIZATION, PATHOLOGIC; OPHTHALMOLOGIC SURGICAL PROCEDURES; PTERYGIUM; TREATMENT OUTCOME;

EID: 44249128000     PISSN: 15420124     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1542-0124(12)70103-9     Document Type: Article

References (316)

1. Moran DJ, Hollows FC. Pterygium and ultraviolet radiation: a positive correlation. Br J Ophthalmol 1984;68:343-6
2. Taylor HR, West SK, Rosenthal FS, et al. Corneal changes associated with chronic UV irradiation. Arch Ophthalmol 1989;107:1481-4
3. Coroneo MT. Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol 1993;77:734-9
4. Ooi JL, Sharma NS, Sharma S, et al. Ultraviolet fluorescence photography: patterns in established pterygia. Am J Ophthalmol 2007;143:97-101
5. Di Girolamo N, Chui J, Coroneo MT, Wakefield D. Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res 2004;23:195-228
6. Carmichael TR. Genetic factors in pterygium in South Africans. S Afr Med J 2001;91:322
7. Booth F. Heredity in one hundred patients admitted for excision of pterygia. Aust N Z J Ophthalmol 1985;13:59-61
8. Zhang JD. An investigation of aetiology and heredity of pterygium. Report of 11 cases in a family. Acta Ophthalmol (Copenh) 1987;65:413-6
9. Hecht F, Shoptaugh MG. Winglets of the eye: dominant transmission of early adult pterygium of the conjunctiva. J Med Genet 1990; 27:392-4
10. Goyal JL, Rao VA, Srinivasan R, Agrawal K. Oculocutaneous manifestations in xeroderma pigmentosa. Br J Ophthalmol 1994;78:295-7
11. Kau HC, Tsai CC, Hsu WM, et al. Genetic polymorphism of hOGG1 and risk of pterygium in Chinese. Eye 2004;18:635-9
12. Tsai YY, Lee H, Tseng SH, et al. Null type of glutathione S-transferase M1 polymorphism is associated with early onset pterygium. Mol Vis 2004;10:458-61
13. Tsai YY, Bau DT, Chiang CC, et al. Pterygium and genetic polymorphism of DNA double strand break repair gene Ku70. Mol Vis 2007;13:1436-40
14. Tsai YY, Lee H, Tseng SH, et al. Evaluationof TNF-alpha and IL-1beta polymorphisms in Taiwan Chinese patients with pterygium. Eye 2005;19:571-4
15. Tsai YY, Chang KC, Lee H, et al. Effect of p53 codon 72 polymorphism on p53 protein expression in pterygium. Clin Experiment Ophthalmol 2005;33:60-2
16. Tsai YY, Cheng YW, Lee H, et al. No association of p53 codon 72 and p2l codon 31 polymorphisms in Taiwan Chinese patients with pterygium. Br J Ophthalmol 2004;88:975-6
17. Weiss JM, Goode EL, Ladiges WC, Ulrich CM. Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature. Mol Carcinog 2005;42:127-41
18. Tsai YY, Cheng YW, Lee H, et al. Oxidative DNA damage in pterygium. Mol Vis 2005;11:71-5
19. Kerb R, Brockmoller J, Reum T, Roots I. Deficiency of glutathione S-transferases T1 and M1 as heritable factors of increased cutaneous UV sensitivity. J Invest Dermatol 1997;108:229-32
20. Board PG. Biochemical genetics of glutathione-S-transferase in man. Am J Hum Genet 1981;33:36-43
21. Strange RC, Fryer AA. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ 1999:148:231-49
22. Featherstone C, Jackson SP. Ku, a DNA repair protein with multiple cellular functions? Mutat Res 1999;434:3-15
23. Gullo C, Au M, Feng G, Teoh G. The biology of Ku and its potential oncogenic role in cancer. Biochim Biophys Acta 2006;1765:223-34
24. Elahi MM, Naseem KM, Matata BM. Nitric oxide in blood. The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease. FEBS J 2007;274:906-23
25. Cejkova J, Stipek S, Crkovska J, et al. UV Rays, the prooxidant/ antioxidant imbalance in the cornea and oxidative eye damage. Physiol Res 2004;53:1-10
26. Nishigori C. Cellular aspects of photocarcinogenesis. Photochem Photobiol Sci 2006;5:208-14
27. Wlaschek M, Tantcheva-Poor I, Naderi L, et al. Solar UV irradiation and dermal photoaging. J Photochem Photobiol B 2001;63:41-51
28. Truscott RJ. Age-related nuclear cataract-oxidation is the key. Exp Eye Res2005;80:709-25
29. Algvere PV, Marshall J, Seregard S. Age-related maculopathy and the impact of blue light hazard. Acta Ophthalmol Scand 2006;84:4-15
30. Izzotti A, Bagnis A, Sacca SC. The role of oxidative stress in glaucoma. Mutat Res 2006;612:105-14
31. Buddi R, Lin B, Atilano SR, et al. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem 2002;50:341-51
32. Cejkova J, Vejrazka M, Platenik J, Stipek S. Age-related changes in superoxide dismutase, glutathione peroxidase, catalase and xanthine oxidoreductase/xanthine oxidase activities in the rabbit cornea. Exp Gerontol 2004;39:1537-43
33. Cejkova J, Stipek S, Crkovska J, Ardan T. Changes of superoxide dismutase, catalase and glutathione peroxidase in the corneal epithelium after UVB rays. Histochemical and biochemical study. Histol Histopathol 2000;15:1043-50
34. Perra MT, Maxia C, Corbu A, et al. Oxidative stress in pterygium: relationship between p53 and 8-hydroxydeoxyguanosine. Mol Vis 2006;12:1136-42
35. Kau HC, Tsai CC, Lee CE et al. Increased oxidative DNA damage, 8-hydroxydeoxy- guanosine, in human pterygium. Eye 2006;20:826-31
36. Lu L, Wang R, Song X. [Pterygium and lipid peroxidation]. Zhonghua Yan Ke Za Zhi 1996;32:227-9
37. Shen A, Ye Y, Wang X, et al. Raman scattering properties of human pterygium tissue. J Biomed Opt 2005;10:024036
38. Brown DJ, Lin B, Chwa M, et al. Elements of the nitric oxide pathway can degrade TIMP-1 and increase gelatinase activity. Mol Vis 2004;10:281-8
39. Di Girolamo N, Wakefield D, Coroneo MT. Differential expression of matrix metalloproteinases and their tissue inhibitors at the advancing pterygium head. Invest Ophthalmol Vis Sci 2000;41:4142-9
40. Di Girolamo N, McCluskey P, Lloyd A, et al. Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells. Invest Ophthalmol Vis Sci 2000;41:671-9
41. Di Girolamo N, Coroneo MT, Wakefield D. Active matrilysin (MMP-7) in human pterygia: potential role in angiogenesis. Invest Ophthalmol Vis Sci 2001;42:1963-8
42. Lee DH, Cho HJ, Kim JT, et al. Expression of vascular endothelial growth factor and inducible nitric oxide synthase in pterygia. Cornea 2001;20:738-42
43. Ozdemir G, Inanc F, Kilinc M. Investigation of nitric oxide in pterygium. Can J Ophthalmol 2005;40:743-6
44. Kon K, Fujii S, Kosaka H, Fujiwara T. Nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester retards vascular sprouting in angiogenesis. Microvasc Res 2003;65:2-8
45. Ziche M, Morbidelli L, Masini E, et al. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 1994;94:2036-44
46. Paunel AN, Dejam A, Thelen S, et al. Enzyme-independent nitric oxide formation during UVA challenge of human skin: characterization, molecular sources, and mechanisms. Free Radic Biol Med 2005;38:606-15
47. Gonzalez Maglio DH, Paz ML, Ferrari A, et al. Skin damage and mitochondrial dysfunction after acute ultraviolet B irradiation: relationship with nitric oxide production. Photodermatol Photoimmunol Photomed 2005;21:311-7
48. Peus D, Meves A, Vasa RA, et al. H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation. Free Radic Biol Med 1999;27:1197-202
49. Peus D, Vasa RA, Meves A, et al. H2O2 is an important mediator of UVB-induced EGF-receptor phosphorylation in cultured keratinocytes. J Invest Dermatol 1998;110:966-71
50. Brenneisen P, Sies H, Scharffetter-Kochanek K. Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events. Ann N Y Acad Sci 2002;973:31-43
51. Di Girolamo N, Coroneo M, Wakefield D. Epidermal growth factor receptor signaling is partially responsible for the increased matrix metalloproteinase 1 expression in ocular epithelial cells after UVB radiation. Am J Pathol 2005;167:489-503
52. Di Girolamo N, Wakefield D, Coroneo MT. UVB-mediated induction of cytokines and growth factors in pterygium epithelial cells involves cell surface receptors and intracellular signaling. Invest Ophthalmol Vis Sci 2006;47:2430-7
53. Di Girolamo N, Coroneo MT, Wakefield D. UVB-elicited induction of MMP-1 expresgon in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. Invest Ophthalmol Vis Sci 2003;44:4705-14.
54. Fisher GJ, Talwar HS, Lin J, et al. Retinoic acid inhibits induction of c-jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. Clin Invest 1998;101:1432-40
55. Liu Z, Xie Y, Zhang M. Overexpression of type I growth factor receptors in pterygium. Chin Med J (Engl) 2002;115:418-21
56. Abeyama K, Eng W, Jester JV, et al. A role for NF-kappaB-dependent gene transactivation in sunburn. Clin Invest 2000;105:1751-9
57. Habib AA, Chatterjee S, Park SK, et al. The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappaB (NF-kappaB)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. J Biol Chem 2001;276:8865-74
58. Ansel JC, Abraham TA, Zivony AS, et al. UV induces human corneal epithelial cell NF-κB activation and results in the production of proinflammatory Cytokines IL-1, IL-6, IL-8, and TNF-α, (abstract). Invest Ophthalmol Vis Sci 2001;42:S575, abstract 3087
59. Sivak JM, Fini ME. MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res 2002;21:1-14
60. Imanishi J, Kamiyama K, Iguchi I, et al. Growth factors: importance in wound heating and maintenance of transparency of the cornea. Prog Retin Eye Res 2000;19:113-29
61. Wilson SE, Mohan RR, Ambrosio R, Jr, et al. The corneal wound healing response: cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog Retin Eye Res 2001; 20:625-37
62. Kennedy M, Kim KH, Harten B, et al. Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells. Invest Ophthalmol Vis Sci 1997;38:2483-91
63. Ley RD, Miska KB, Kusewitt DF. Photoreactivation of ultraviolet radiation-induced basic fibroblast growth factor (bFGF) and the role of bFGF in corneal lesion formation in Monodelphis domestica. Environ Mol Mutagen 2001;38:175-9
64. Bielenberg DR, Bucana CD, Sanchez R, et al. Molecular regulation of UNB-induced cutaneous angiogenesis. J Invest Dermatol 1998;111:864-72
65. Blaudschun R, Sunderkotter C, Brenneisen P, et al. Vascular endothetial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo. Br J Dermatol 2002;146:581-7
66. Di Girolamo N, Kumar RK, Coroneo MT, Wakefield D. UVB-mediated induction of interleukin-6 and -8 in pterygia and cultured human pterygium epithelial cells. Invest Ophthalmol Vis Sci 2002;43:3430-7
67. Nolan TM, DiGirolamo N, Sachdev NH, et al, The role of ultraviolet irradiation and heparin-binding epidermal growth factor-like growth factor in the pathogenesis of pterygium. Am J Pathol 2003;162:567-74
68. Baba H, Uchiwa H, Watanabe S. UVB irradiation increases the release of SCF from human epidermal cells. J Invest Dermatol 2005;124:1075-7
69. Onoue S, Kobayashi T, Takemoto Y, et al. Induction of matrix metalloproteinase-9 secretion from human keratinocytes in culture by ultraviolet B irradiation. J Dermatol Sci 2003;33: 105-11
70. Koivukangas V, Kallioinen M, Autio-Harmainen H, Oikarinen A. UV irradiation induces the expression of gelatinases in human skin in vivo. Acta Derm Venereol 1994;74:279-82
71. Solomon A, Li DQ, Lee SB, Tseng SC. Regulation of collagenase, stromelysin, and urokinase-type plasminogen activator in primary pteryium body fibroblasts by inflammatory cytokines. Invest Ophthalmol Vis Sci 2000;41:2154-63
72. Pinkerton OD, Hokama Y, Shigemura LA. Immunologic basis for the pathogenesis of pterygium. Am J Ophthalmol 1984;98:225-8
73. Liu L, Yang D. Immunological studies on the pathogenesis of pterygium. Chin Med Sci J 1993;8:84-8
74. Kria L, Ohira A, Amemiya T. Immunohistochemical localization of basic fibroblast growth factor, platelet derived growth factor, transforming growth factor-beta and tumor necrosis factor-alpha in the pterygium. Acta Histochem 1996;98:195-201
75. Wen Z, Liu Z. [The abnormal expression of interleukine-1 family in pterygium]. Yan Ke Xue Bao 2003; 19:133-6
76. Butrus SI, Ashraf MF, Laby DM, et al. Increased numbers of mast cells in pterygia. Am J Ophthalmol 1995;119:236-7
77. Nakagami T, Watanabe I, Murakami A, et al. Expression of stem cell factor in pterygium. Jpn J Ophthalmol 2000;44:193-7
78. Nolan TM, Di Girolamo N, Coroneo MT, Wakefield D. Proliferative effects of heparin-binding epidermal growth factor-like growth factor on pterygium epithelial cells and fibroblasts. Invest Ophthalmol Vis Sci 2004;45:110-3
79. Hoppenreijs VP, Pels E, Vrensen GF, et al. Platelet-derived growth factor: receptor expression in corneas and effects on corneal cells. Invest Ophthalmol Vis Sci 1993;34:637-49
80. Nishida T, Nakamura M, Mishima H, Otori T. Interleukin 6 promotes epithelial migration by a fibronectin-dependent mechanism. J Cell Physiol 1992; 153:1-5
81. Nishida T, Nakamura M, Mishima H, et al. Interleukin 6 facilitates corneal epithelial wound closure in vivo. Arch Ophthalmol 1992;110:1292-4
82. Nakamura M, Nishida T. Differential effects of epidermal growth factor and interleukin 6 on corneal epithelial cells and vascular endothelial cells. Cornea 1999;18:452-8
83. Andresen JL, Ehlers N. Chemotaxis of human keratocytes is increased by platelet-derived growth factor-BB, epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, and transforming growth factor-beta. Curr Eye Res 1998;17:79-87
84. Seifert P, Sekundo W. Capillaries in the epithelium of pterygium. Br J Ophthalmol 1998;82:77-81
85. Yoshida S, Ono M, Shono T, et al. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 1997;17:4015-23
86. Abramovitch R, Neeman M, Reich R, et al. Intercellular communication between vascular smooth muscle and endothelial cells mediated by heparin-binding epidermal growth factor-like growth factor and vascular endothelial growth factor. FEBS Lett 1998;425:441-7
87. Jin J, Guan M, Sima J, et al. Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia. Cornea 2003;22:473-7
88. Ma DH, Yao JY, Yeh LK, et al. In vitro antiangiogenic activity in ex vivo expanded human limbocorneal epithelial cells cultivated on human amniotic membrane. Invest Ophthalmol Vis Sci 2004;45:2586-95
89. Aspiotis M, Tsanou E, Gorezis S, et al. Angiogenesis in pterygium: study of microvessel density, vascular endothelial growth factor, and thrombospondin-1. Eye 2007;21:1095-101
90. Lavker RM, Tseng SC, Sun TT. Corneal epithelial stem cells at the limbus: looking at some old problems from a new angle. Exp Eye Res 2004;78:433-46
91. Dushku N, Reid TW. Immunohistochemical evidence that human pterygia originate from an invasion of vimentin-expressing altered limbal epithelial basal cells. Curr Eye Res 1994;13:473-81
92. Ye J, Song YS, Kang SH, et al. involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium. Eye 2004;18:839-43
93. Nakamura T, Ishikawa F, Sonoda KH, et al. Characterization and distribution of bone marrow-derived cells in mouse cornea. Invest Ophthalmol Vis Sci 2005;46:497-503
94. Yamagami S, Ebihara N, Usui T, et al. Bone marrow-derived cells in normal human corneal stroma. Arch Ophthalmol 2006;124:62-9
95. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434-8
96. Song YS, Ryu YH, Choi SR, Kim JC. The involvement of adult stem cells originated from bone marrow in the pathogenesis of pterygia. Yonsei Med J 2005;46:687-92
97. Ye J, Kook KH, Yao K. Temporary amniotic membrane patch for the treatment of primary pterygium: mechanisms of reducing the recurrence rate. Graefes Arch Clin Exp Ophthalmol 2006;244:583-8
98. Lee JK, Kim JC. Progenitor cells in healing after pterygium excision. Yonsei Med J 2007;48:48-54
99. Alviano F, Fossati V, Marchionni C, et al. Term amniotic membrane is a high throughput source for multipotent mesenchymal stem cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol 2007;7:11
100. Lee JK, Song YS, Ha HS, et al. Endothelial progenitor cells in pterygium pathogenesis. Eye 2007;21:1186-93
101. Chui J, Di Girolamo N, Coroneo MT, Wakefield D. The role of substance p in the pathogenesis of pterygia. Invest Ophthalmol Vis Sci 2007;48:4482-9
102. Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn 2005;233:706-20
103. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005:24:5764-74
104. Kase S, Osaki M, Sato I, et al. Immunolocalisation of E-cadherin and beta-catenin in human pterygium. Br J Ophthalmol 2007; 91:1209-12
105. Kato N, Shimmura S, Kawakita T, et al. Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Invest Ophthalmol Vis Sci 2007;48:1511-7
106. Strutz F, Zeisberg M, Ziyadeh FN, et al. Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney Int 2002;61:1714-28
107. Hudson LG, Choi C, Newkirk KM, et al. Ultraviolet radiation stimulates expression of Snail family transcription factors in keratinocytes. Mol Carcinog 2007; 46:257-68
108. Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002;110:341-50
109. SundaRaj N, Rizzo JD, Anderson SC, Gesiotto JP. Expression of vimentin by rabbit corneal epithelial cells during wound repair. Cell Tissue Res 1992;267:347-56
110. Li W Hiyashida Y, He H, et al. The fate of limbal epithelial progenitor cells during explant culture on intact amniotic membrane. Invest Ophthalmol Vis Sci 2007;48:605-13
111. Kawakita T, Espana EM, He H, et al. Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure. Am J Pathol 2005; 167:381-93
112. Touhami A, Di Pascuale MA, Kawatika T, et al. Characterisation of myofibroblasts in fibrovascular tissues of primary and recurrent pterygia. Br J Ophthalmol 2005;89:269-74
113. Ishii G, Sangai T, Sugiyama K, et al. In vivo characterization of bone marrow-derived fibroblasts recruited into fibrotic lesions. Stem Cells 2005;23:699-706
114. Sevel D, Sealy R. Pterygia and carcinoma of the conjunctiva. Trans Ophthalmol Soc UK 1969;88:567-78
115. Tan DT, Liu YP, Sun L, Flow cytometry measurements of DNA content in primary and recurrent pterygia. Invest Ophthalmol Vis Sci 2000;41:1684-6
116. Tan DT, 'rang WY, Liu YP et al, Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium. Br J Ophthalmol 2000;84:212-6
117. Tsironi S, Ioachim E, Machera M, et al. Presence and possible significance of immunohistochemically demonstrable metallothionein expression in pterygium versus pinguecula and normal conjunctiva. Eye 2001;15(Pt 1):89-96
118. Ueda Y, Kanazawa S, Kitaoka T, et al. Immunohistochemical study of p53, p21 and PCNA in pterygium. Acta Histochem 2001;103:159-65
119. Kase S. Takahashi S, Sato I, et al. Expression of p27(KIP1) and cyclin D1, and cell proliferation in human pterygium. Br J Ophthalmol 2007;91:958-61
120. Chen JK, Tsai RJ, Lin SS. Fibroblasts isolated from human pterygia exhibit transformed cell characteristics. In Vitro Cell Dev Biol Anim 1994;30A:243-8
121. Solomon A, Grueterich M, Li DQ, et al. Overexpression of insulin-like growth factor-binding protein-2 in pterygium body fibroblasts. Invest Ophthalmol Vis Sci 2003;44:573-80
122. Wong YW, Chew J, Yang H, et al. Expression of insulin-like growth factor binding protein-3 in pterygium tissue. Br J Ophthalmol 2006;90:769-72
123. Lee KW, Cohen P. Nuclear effects: unexpected intracellular actions of insulin-like growth factor binding protein-3. J Endocrinol 2002;175:33-40
124. Peiretti E, Dessi S, Putzolu M, Fossarello M. Hyperexpression of low-density lipoprotein receptors and hydroxy-methylglutaryl-coenzyme A-reductase in human pinguecula and primary pterygium. Invest Ophthalmol Vis Sci 2004;45:3982-5
125. Peiretti E, Dessi S, Mulas ME et al. Fibroblasts isolated from human pterygia exhibit altered lipid metabolism characteristics. Exp Eye Res 2006;83:536-42
126. Dushku N, Reid TW. P53 expression in altered limbal basal cells of pingueculae, pterygia, and limbal tumors. Curr Eye Res 1997;16:1179-92
127. Spandidos DA, Sourvinos G, Kiaris H, Tsamparlakis J. Microsatellite instabilityl and loss of heterozygosity inhuman pterygia. Br J Ophthalmol 1997;81:493-6
128. Tsai YY, Cheng YW, Lee H, et al. P53 gene mutation spectrum and the relationship between gene mutatión and protein levels in pterygium. Mol Vis 2005;11:50-5.
129. Detorakis ET, Jafiropoulos A, Arvanitis DA, Spandidos DA. Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia. Eye 2005;19:210-4
130. Chen PL, Cheng YW, Chiang CC, et al. Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA methyltransferase 3b. Mol Vis 2006;12:1411-6
131. Detorakis ET, Sourvinos G, Tsamparlakis J, Spandidos DA. Evaluation of loss of heterozygosity and microsatellite instability in human pterygium: clinical correlations. Br J Ophthalmol 1998;82:1324-8
132. Schneider BG, Sahni D, Torres JC, et al. MLH1 and MSH2 expression in pterygia. Cornea 2007;26:468-72
133. Drouin R, Therrien JP. UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53. Photochem Photobiol 1997;66:719-26
134. Tan DT, Lim AS, Goh HS, Smith DR. Abnormal expression of the p53 tumor suppressor gene in the conjunctiva of patients with pterygium. Am J Ophthalmol 1997;123:404-5
135. Weinstein O, Rosenthal G, Zirkin H, et al. Overexpression of p53 tumor suppressor gene in pterygia. Eye 2002;16:619-21
136. Onur C, Orhan D, Orhan M, et al. Expression of p53 protein in pterygium. Eur J Ophthalmol 1998;8:157-61
137. Chowers I, Pe'er J, Zamir E, et al. Proliferative activity and p53 expression in primary and recurrent pterygia. Ophthalmology 2001;108:985-8
138. Decraene D, Agostinis P, Pupe A, et al. Acute response of human skin to solar radiation: regulation and function of the p53 protein, J Photochem Photobiol B 2001;63:78-83
139. Shimmura S, Ishioka M, Hanada K, et al. Telomerase activity and p53 expression in pterygia. Invest Ophthalmol Vis Sci 2000;41:1364-9
140. Reisman D, McFadden JW, Lu G. Loss of heterozygosity and p53 expression in pterygium. Cancer Lett 2004;206:77-83
141. Robertson KD, Uzvolgyi E, Liang G, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res 1999;27:2291-8
142. Ramalho FS, Maestri C, Ramalho LN, et al. Expression of p63 and p16 in primary and recurrent pterygia. Graefes Arch Clin Exp Ophthalmol 2006;244:1310-4
143. Thoft RA, Friend J, The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci 1983;24:1442-3
144. Muller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res 2003;76:521-42
145. Benrath J, Zimmermann M, Gillardon F. Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. Neurosci Lett 1995;200:17-20
146. Ansel JC, Armstrong CA, Song I, et al. Interactions of the skin and nervous system. J Investig Dermatol Symp Proc 1997;2:23-6
147. Luger TA, Lotti T. Neuropeptides: role in inflammatory skin diseases. J Eur Acad Dermatol Venereol 1998;10:207-11
148. Legat FJ, Griesbacher T, Schicho R, et al. Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats. Neurosci Lett 2002;329:309-13
149. van der Zypen F, van der Zypen E, and Daicker B. ltrastructural studies on the pterygium. II. Connective tissue, vessels and nerves of the conjunctival part (author's transl)]. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1975;193:177-87
150. Karukonda SR, Thompson HW, Beuerman RW, et al. Cell cycle kinetics in pterygium at three latitudes. Br J Ophthalmol 1995;79:313-7
151. Kobayashi A, Sugiyama K. In vivo corneal confocal microscopic findings of palisades of Vogt and its underlying limbal stroma. Cornea 2005;24:435-7
152. Ueda S, del Cerro M, LoCascio JA, Aquavella JV. Peptidergic and catecholaminergic fibers in the human corneal epithelium. An immunohistochemical and electron microscopic study. Acta Ophthalmol Suppl 1989;192:80-90
153. Tran MT, Lausch RN, Oakes JE. Substance P differentially stimulates IL-8 synthesis in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2000;41:3871-7
154. Tran MT, Ritchie MH, Lausch RN, Oakes JE. Calcitonin gene-related peptide induces IL-8 synthesis in human corneal epithelial cells. J Immunol 2000;164:4307-12
155. Reid TW, Murphy CJ, Iwahashi CK, et al. Stimulation of epithelial cell growt1h by the neuropeptide substance P. J Cell Biochem 1993;52:476-85
156. Nishida T, Nakamura M, Ofuji K, et al. Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea. J Cell Physiol 1996;169:159-66
157. Nakamura M, Ofuji K, Chikama T, Nishida T. The NKI receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1. Br J Pharmacol 1997;120:547-52
158. Mikulec AA, Tanelian DL. CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation. J Ocul Pharmacol Ther 1996;12:417-23
159. Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res 1994; 59:597-605
160. Harrison NK, Dawes KE, Kwon OJ, et al. Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis. Am J Physiol 1995;268(2 Pt 1):L278-83
161. Parenti A, Amerini S, Ledda F, et al. The tachykinin NK1 receptor mediates the migration-promoting effect of substance P on human skin fibroblasts in culture. Naunyn Schmiedebergs Arch Pharmacol 1996;353:475-81
162. Kahler CM, Sitte BA, Reinisch N, Wiedermann CJ. Stimulation of the chemotactic migration of human fibroblasts by substance P. Eur J Pharmacol 1993;249:281-6
163. Yule KA, White SR. Migration of 3T3 and lung fibroblasts in response to calcitonin gene-related peptide and bombesin. Exp Lung Res 1999;25:261-73
164. Haegerstrand A, Dalsgaard CJ, Jonzon B, et al. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. Proc Natl Acad Sci U S A 1990;87:3299-303
165. Yaylali V, Ohta T, Kaufman SC, et al. In vivo confocal imaging of corneal neovascularization. Cornea 1998;17:646-53
166. Ayaki K, Ohashi Y, Kinoshita S, et al. Epithelial wound healing in the denervated cornea. Curr Eye Res 1994;13:203-11
167. Brown SM, Lamberts DW, Reid TW, et al. Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike growth factor 1. Arch Ophthalmol 1997;115:926-7
168. Stapleton F, Chui J, Tan M, Coroneo M. Effect of pterygium on corneal sensitivity (abstract). Clin Experiment Ophthalmol 2002;30(Suppl):A26
169. Hirst LW. The treatment of pterygium. Surv Ophthalmol 2003:48:145-80
170. Ang LP, Chua JL, Tan DT. Current concepts and techniques in pterygium treatment. Curr Opin Ophthalmol 2007;18:308-13
171. Farrah JJ, Lee GA, Greenrod E, Vieira J. Outcomes of autoconjunctival grafting for primary pterygia when performed by consultant compared with trainee ophthalmologists. Clin Experiment Ophthalmol 2006; 34:857-60
172. Allan BD, Short P, Crawford GJ, et al. Pterygium excision with conjunctival autografting: an effective and safe technique. Br J Ophthalmol 1993;77:698-701
173. Vrabec MP, Weisenthal RW, Elsing SH. Subconjunctival fibrosis after conjunctival autograft. Cornea 1993;12:181-3
174. Sridhar MS, Bansal AK, Rao GN. Surgically induced necrotizing scleritis after pterygium excision and conjunctival autograft. Cornea 2002;21:305-7
175. Berman B, Villa AM, Ramirez CC. Mechanisms of action of new treatment modalities for actinic keratosis. J Drugs Dermatol 2006;5:167-73
176. Rubinfeld RS, Pfister RR, Stein RM, et al. Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology 1992;99:1647-54
177. Rubinfeld RS. Long-term results after bare sclera pterygium resection with excimer smoothiqg and local application of mitomycin C. Cornea 2006;25:758; author reply, 758-9
178. Akinci A, Zilelioglu O. Comparison of linibal-conjunctival autograft and intraoperative 0.02% mitomycin-C for treatment of primary pterygium. Int Ophthalmol 2007;27:281-5
179. Pikkel J, Porges Y, Ophir A. Halting pterygium recurrence by postoperative 5-fluorouracil. Cornea 2001;20:168-71
180. a Khaw PT, Doyle JW, Sherwood MB, et al. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol 1993;111:263-7
181. b Khaw PT, Sherwood MB, Doyle JW, et al. Intraoperative and postoperative treatment with 5-fluorouracil and mitomycin-C: long-term effects in vivo on subconjunctival and scleral fibroblasts. Int. Ophthalmol 1992;16(4-5):381-5
182. Pherwani A, Vakil V, Eatamadi H, et al. Postoperative subconjunctival 5-fluorouracil in the management of recurring pterygium. Br J Ophthalmol 2007;91:398-9
183. Akarsu C, Taner P and Ergin A. 5-Fluorouracil as chemoadjuvant for primary pterygium surgery: preliminary report. Cornea 2003; 22:522-6
184. Bekibele CO, Baiyeroju AM, Ajayi BG. 5-fluorouracil vs. beta-irradiation in the prevention of pterygium recurrence. Int J Clin Pract 2004;58:920-3
185. Abraham LM, Selva D, Casson R, Leibovitch I. The clinical applications of fluorouracil in ophthalmic practice. Drugs 2007;67:237-55
186. Berman B, Villa AM, Ramirez CC. Novel opportunities in the treatment and prevention of scarring. J Cutan Med Surg 2004;8 (Suppl 3):32-6
187. Chen MA, Davidson TM. Scar management: prevention and treatment strategies. Curr Opin Otolaryngol Head Neck Surg 2005;13:242-7
188. Kria L, Ohira A, Amemiya T. Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA analysis. Graefes Arch Clin Exp Ophthalmol 1998;236:702-8
189. Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 2007;6:273-86
190. Phillips GD, Stone AM, Jones BD, et al. Vascular endothelial growth factor (rhVEGF165) stimulates direct angiogenesis in the rabbit cornea. In Vivo 1994;8:961-5
191. Kenyon BM, Voest EE, Chen CC, et al. A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci 1996;37:1625-32
192. Ranieri G, Patruno R, Ruggieri E, et al. Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. Curr Med Chem 2006; 13:1845-57
193. Takeda AL, Colquitt J, Clegg AJ, Jones J. Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review. Br J Ophthalmol 2007;91:1177-82
194. Camilo ER, Paes JP, Godinho TCS, et al. The use of intra-operatorial avastin as coadjutant in the surgical treatment of recurrence pterygium (abstract). Invest Ophthalmol Vis Sci 2007;48(Suppl): Poster session 521, S5295/B506
195. Kusaka M, Sudo K, Fujita T, et al. Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent. Biochem Biophys Res Commun 1991;174:1070-6
196. Antoine N, Greimers R, De Roanne C, et al. AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. Cancer Res 1994;54:2073-6
197. Yeh JR, Ju R, Brdlik CM, et al. Targeted gene disruption of methionine aminopeptidase 2 results in an embryonic gastrulation defect and endothelial cell growth arrest. Proc Natl Acad Sci U S A 2006;103:10379-84
198. Sin N, Meng L, Wang MQ, et al. The anti-angiogenic agent fumagillin
199. Zhang Y, Griffith EC, Sage J, et al. Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1/CIP1. Proc Natl Acad Sci U S A 2000;97:6427-32
200. Joussen AM, Beecken WD, Moromizato Y, et al. Inhibition of inflammatory corneal angiogenesis by TNP-470. Invest Ophthalmol Vis Sci 2001;42:2510-6
201. Kria L, Chira A, Amemiya T. TNP-470 (a fungus-derived inhibitor of angiogenesis) reduces proliferation of cultured fibroblasts isolated from primary pterygia: a possible drug therapy for pterygia. Curr Eye Res 1998; 17:986-93
202. Yoshio Y, Miyazaki M, Abe K, et al. TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model. Kidney Int 2004;66:1677-85
203. Wang YQ, Ikeda K, Ikebe T, et al. inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats. Hepatology 2000;32:980-9.
204. Selvakumar P, Lakshmikuttyamma A, Dimmock JR, Sharma RK. Methionine aminopeptidase 2 and cancer. Biochim Biophys Acta 2006;1765:148-54
205. Bhargava P, Marshall JL, Rizvi N, et al. A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer. Clin Cancer Res 1999;5:1989-95
206. Logothetis CJ, Wu KK, Finn LD, et al. Phase 1 trial of the angiogenesis inhibitor TNP-470 for progressive androgen-independent prostate cancer. Clin Cancer Res 2001;7:1198-203
207. Figg WD, Pluda JM, Lush RM, et al. The pharmacokinetics of TNP-470, a new angiogenesis inhibitor. Pharmacotherapy 1997;17:91-7
208. Bernier SG, Lazarus DD, Clark E, et al. A methionine amino-peptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. Proc Natl Acad Sci USA 2004;101:10768-73
209. Hannig G, Bernier SG, Hoy tJG, et al. Suppression of inflammation and structural damage in experimental arthritis through molecular targeted therapy with PPI-2458. Arthritis Rheum 2007;56:850-60
210. Peiretti E, Dessi S, Mulas C, et al. Modulation of cholesterol homeostasis by antiproliferative drugs in human pterygim fibroblasts. Invest Ophthalmol Vis Sci 2007;48:3450-8
211. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000;405:421-4
212. Sarayba MA, Li L, Tungsiripat T, et al. Inhibition of corneal neovascularization by a peroxisome proliferator-activated receptor-gamma ligand. Exp Eye Res 2005;80:435-42
213. Keshamouni VG, Arenberg DA, Reddy RC, et al. PPAR-gamma activation inhibits angiogenesis by blocking ELR+CXC chemokine production in non-small cell lung cancer. Neoplasia 2005;7:294-301
214. Yamakawa K, Hosoi M, Koyama H, et al. Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells. Biochem Biophys Res Commun 2002;271:571-4
215. Huang PH, Sata M, Nishimatsu H, et al. Pioglitazone ameliorates endothelial dysfunction and restores ischemia-induced angiogenesis in diabetic mice. Biomed Pharmacother 2007 July 20 [epub ahead of print]
216. Wang CH, Ting MK, Verma S, et al. Pioglitazone increases the numbers and improves the functional capacity of endothelial progenitor cells in patients with diabetes mellitus. Am Heart J 2006;152:1051.e1-8
217. Freudlsperger C, Moll I, Schumacher U, Thies A. Anti-proliferative effect of peroxisome proliferator-activated receptor gamma agonists on human malignant melanoma cells in vitro. Anticancer Drugs 2006;17:325-32
218. Burton JD, Castillo ME, Goldenberg DM, Blumenthal RD. Peroxisome proliferator-activated receptor-gamma antagonists exhibit potent antiproliferative effects versus many hematopoietic and epithelial cancer cell lines. Anticancer Drugs 2007; 18:525-34
219. Neuhaus P, Klupp J, Langrehr JM. mTOR inhibitors: an overview. Liver Transpl 2001;7:473-84.
220. Weischer M, Rocken M, Berneburg M. Calcineurin inhibitors and rapamycin: cancer protection or promotion? Exp Dermatol 2007;16:385-93
221. Seeliger H, Guba M, Kleespies A, et al. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 2007;26:611-21
222. Olsen TW, Benegas NM, Joplin AC, et al. Rapamycin inhibits coneal allograft rejection and neovascularization. Arch Ophthalmol 1994; 112:1471-5
223. Gao H, Shi WY, Xie LX, Wang SG. [Sustained rapamycin drug delivery system in prevention of high risk corneal allograft rejection and neovascularization in rabbits]. Zhonghua Yan Ke Za Zhi 2006; 42:6-11
224. Shi W, Gao H, Xie L, Wang S. Sustained intraocular rapamycin delivery effectively prevents high-risk corneal allograft rejection and neovascularization in rabbits. Invest Ophthalmol Vis Sci 2006;47:3339-44
225. Kwon YS, Kim JC. Inhibition of corneal neovascularization by rapamycin. Exp Mol Med 2006;38:173-9
226. Kwon YS, Hong HS, Kim JC, et al. inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo. Invest Ophthalmol Vis Sci 2005;46:454-60
227. Powers MR, Qu Z, O'Brien B, et al. Immunolocalization of bFGF in pterygia: association with mast cells. Cornea 1997; 16:545-9
228. Nakagami T, Murakami A, Okisaka S, Ebihara N. Mast cells in pterygium: number and phenotype. Jpn J Ophthalmol 1999;43:75-9
229. Ribatti D, Nico B, Maxia C, et al. Neovascularization and mast cells with tryptase activity increase simultaneously in human pterygium. J Cell Mol Med 2007; 11:585-9
230. Pflugfelder SC. Anti-inflammatory therapy for dry eye. Am J Ophthalmol 2004;137:337-42
231. Tatlipinar S, Akpek EK. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol 2005;89:1363-7
232. Hernandez GL, Volpert OV, Iniguez MA, et al. Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 2001; 193:607-20
233. Benelli U, Ross JR, Nardi M, Klintworth GK. Corneal neovascularization induced by xenografts or chemical cautery. Inhibition by cyclosporin A. Invest Ophthalmol Vis Sci 1997;38:274-82
234. Hercules LA, Viveiros MM, Schellini SA, et al. [Exposure of Tenon's capsule fibroblasts of pterygium to cyclosporin 0.05%]. Arq Bras Oftalmol 2006;69:831-5
235. Leonardi A, DeFranchis G, Fregona IA, et al. Effects of cyclosporin A on human conjunctival fibroblasts. Arch Ophthalmol 2001;119:1512-7
236. Bagci G, Yucel I, Duranoglu Y. The effect of cyclosporin A on cultured rabbit subconjunctival fibroblast proliferation: Ophthalmologica 1999;213:114-9
237. Hu Y, Adan ES, Matsumoto Y, et al. Conjunctival in vivo confocal scanning laser microscopy in patients with atopic keratoconjunctivitis. Mol Vis 2007; 13:1379-89
238. Yarosh DB, Pena AV, Nay SL, et al. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol 2005; 125:1020-5
239. Canning MT, Nay SL, Pena AV, Yarosh DB. Calcineurin inhibitors reduce nuclear localization of transcription factor NEAT in UV irradiated keratinocytes and reduce DNA repair. J Mol Histol 2006;37:285-91
240. Strong B, Farley W, Stern ME, Pflugfelder SC. Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjunctivitis sicca. Cornea 2005;24:80-5
241. Minguez E, Tiestos MT, Cristobal JA, et al. [Intraocular absorption of cyclosporin A eyedrops]. J Fr Ophtalmol 1992; 15:263-7
242. Acheampong AA, Shackleton M, Tang-Liu DD, et al. Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and beagle dogs. Curr Eye Res 1999;18:91-103
243. Wu H, Chen G. [Cyclosporine A and thiotepa in preveirtion of postoperative recurrence of pterygium]. Yan Ke Xue Bao 1999; 15:91-2
244. Gitter BD, Waters DC, Threlkeld PG, et al. Cyclosporin A is a substance P (tachykinin NK1) receptor antagonist. Eur J Pharmacol 1995;289:439-46
245. Iurlaro M, Vacca A, Minischetti M, et al. Antiangiogenesis by cyclosporine. Exp Hemiatol 1998;26:1215-22
246. Yang G, Mcguro T, Hong C, et al. Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis. J Mol Cell Cardiol 2001;33:1505-14
247. Kaminska B, Gaweda-Walerych K, Zawadzka M. Molecular mechanisms of neuroprotective action of immunosuppressants-facts and hypotheses. J Cell Mol Med 2004;8:45-58
248. Parmar S, Platanias LC. Interferons: mechanisms of action and clinical applications. Curr Opin Oncol 2003;15:431-9
249. de Weerd NA, Samarajiwa SA, Hertzog PJ. Type I interferon receptors: biochemistry and biological functions. J Biol Chem 2007; 282:20053.7
250. Schechter BA, Schrier A, Nagler RS, et al. Regression of presumed primary conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b. Cornea 2002;21:6-11
251. Karp CL, Moore JK, Rosa RH, Jr. Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b. Ophthalmology 2001;108:1093-8
252. Fuchsluger TA, Hintschich C, Steuhl KP, Meller D. [Adjuvant topical interferon-alpha-2b treatment in epithelial tumors of the ocular surface]. Ophthalmologe 2006;103):124-8
253. Huerva V, Sanchez MC, Mangues I. Tumor-volume increase at beginning of primary treatment with topical interferon alpha 2-beta in a case of conjunctiva-cornea intraepithelial neoplasia. J Ocul Pharmacol Ther 2007;23:143-5
254. de Keizer RJ, de Wolff-Rouendaal D. Topical alpha-interferon in recurrent conjunctival papilloma. Acta Ophthalmol Scand 2003;81:193-6
255. Falco LA, Gruosso PJ, Skolnick K, Bejar L. Topical interferon alpha 2 beta therapy in the management of conjunctival papilloma. Optometry 2007;78:162-6
256. Nemet AY, Sharma V, Benger R. Interferon alpha 2b treatment for residual ocular surface squamous neoplasia unresponsive to excision, cryotherapy and mitomycin-C. Clin Experiment Ophthalmol 2006;34:375-7
257. Holcombe DJ, Lee GA. Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia. Am J Ophthalmol 2006;142:568-71
258. Blasi MA, Gherlinzoni E Calvisi G, et al. Local chemotherapy with interferon-alpha for conjunctival mucosa-associated lymphoid tissue lymphoma: a preliminary report. Ophthalmology 2001;108:559-62
259. Ross JJ, Tu KL, Damato BE. Systemic remission of non-Hodgkin's lymphoma after intralesional interferon alpha-2b to bilateral conjunctival lymphomas. Am J Ophthalmol 2004;138:672-3
260. Lucas RS. Mortimore R, Sullivan TJ, Walche M. Interferon treatment of childhood conjunctival lymphoma. Br J Ophthalmol 2003;87:1191
261. Finger PT, Reichstein D. Interferon alpha eye drops: treatment of atypical lymphoid hyperplasia with secondary alopecia. Br J Ophthalmol 2007;91:1085-6
262. Aldave AJ, Nguyen A. Ocular surface toxicity associated with topical interferon alpha-2b. Br J Ophthalmol 2007;91:1087-8
263. Esquenazi S. Treatment of early pterygium recurrence with topical administration of interferon alpha-2b. Can J Ophthalmol 2005;40:185-7
264. Toma S, Monteghirfo S, Tasso P, et al. Antiproliferative and synergistic effect of interferon alpha-2a, retinoids and their association in established human cancer cell lines. Cancer Lett 1994;82:209-16
265. Nguyen N, Goldberg M, Pico J, et al. Topical and subcutaneous alpha-interferon fails to suppress corneal neovascularization. Cornea 1995;14:147-51
266. Ruszczak Z, Detmar M, Imcke E, Orfanos CE. Effects of rIFN alpha, beta, and gamma on the morphology, proliferation, and cell surface antigen expression of human dermal microvascular endothelial cells in vitro. J Invest Dermatol 1990;95:693-9
267. Miller JW, Stinson WG, Folkman J. Regression of experimental iris neovascularization with systemic alpha-interferon. Ophthalmology 1993;100:9-14
268. Germain P, Chambon P, Eichele G, et al. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev 2006;58:712-25
269. Nezzar H, Chiambaretta F, Marceau G, et al. Molecular and metabolic retinoid pathways in the human ocular surface. Mol Vis 2007;13:1641-50
270. Tei M, Spurr-Michaud SJ, Tisdale AS, Gipson IK. Vitamin A deficiency alters the expression of mucin geDes by the rat ocular surface epithelium. Invest Ophthalmol Vis Sci 2000;41:82-8
271. Kruse FE, Tseng SC. Retinoic acid regulates clonal growth and differentiation of cultured limbal and peripheral corneal epithelium. Invest. Ophthalmol Vis Sci 1994;35:2405-20
272. Tseng SC, Farazdaghi M. Reversal of conjunctival transdifferentiation by topical retinoic acid. Cornea 1988;7:273-9
273. Kenney MC, Shih LM, Labermeir U, Satterfield D. Modulation of rabbit keratocyte production of collagen, sulfated glycosami-Doglycans and fibronectin by retinol and retinoic acid. Biochim Biophys Acta 1986;889:156-62
274. Kanazawa S, Kitaoka T, Ueda Y, et al. Interaction of zinc and vitamin A on the ocular surface. Graefes Arch Clin Exp Ophthalmol 2002;240):1011-21
275. Rodger FC. The ocular effects of vitamin A deficiency in man in the tropics. Exp Eye Res 1964;15:367-72
276. Pfister RR, Renner ME. The corneal and conjunctival surface in vitamin A deficiency: a scanning electron microscopy study. Invest Ophthalmol Vis Sci 1978;17:874-83
277. Mongan NP, Gutlas LJ. Diverse actions of retinoid receptors in cancer prevention and treatment. Differentiation 2007;75:853-70
278. Gilchrest BA. Treatment of photodamage with topical tretinoin: an overview. J Am Acad Dermatol 1997;36(3 Pt 2):S7-36
279. Herbort CP, Zografos L, Zwingli M, Schoeneich' M. Topical retinoic acid in dysplastic and metaplastic keratinization of corneoconjunctival epithelium. Graefes Arch Clin Exp Ophthalmol 1988;226:22-6
280. Tseng SC, Maumenee AE, Stark W, et al. Topical retinoid treatment for various dry-eye disorders. Ophthalmology 1985;92:717-27
281. Soong HK, Martin NF, Wagoner MD, et al. Topical retinoid therapy for squamous metaplasia of various ocular surface disorders. A multicenter, placebo-controlled double-masked study. Ophthalmology 1988;95:1442-6
282. Orfanos CE, Bauer R. Evidence for anti-inflammatory activities of oral synthetic retinoids: experimental findings and clinical experience. Br J Dermatol 1983;25:55-60
283. Majewski S, Marczak M, Szmurlo A, et al. Retinoids, interferon alpha, 1,25-dihydroxyvitamin D3 and their combination inhibit angiogenesis induced by non-HPV-harboring tumor cell lines. RAR alpha mediates the antiangiogenic effect of retinoids. Cancer Lett 1995;89:117-24
284. Imcke E, Ruszczak Z, Mayer-da Silva A, et al. Cultivation of human dermal microvascular endothelial cells in vitro: immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res 1991;283:149-57
285. Bossenbroek NM, Sulahian TH, Ubels JL. Expression of nuclear retinoic acid receptor and retinoid X receptor mRNA in the cornea and conjunctiva. Curr Eye Res 1998;17:462-9
286. Shams NB, Reddy CV, Watanabe K, et al.Iincreased interleukin-1 activity in the injured vitamin A-deficient cornea. Cornea 1994;13:156-66
287. Pirie A, Werb Z, Burleigh MC. Collagenase and other proteinases in the cornea of the retinol-deficient rat. Br J Nutr 1975;34:297-309
288. Hanazawa S, Takeshita A and Kitano S. Retinoic acid suppression of c-fos gene inhibits expression of tumor necrosis factor-alpha-induced monocyte chemoattractant JE/MCP-1 in clonal osteoblastic MC3T3-El cells. J Biol Chem 1994;269:21379-84
289. Lingen MW, Polverini PJ, Bouck NP. Inhibition of squamous cell carcinoma angiogenesis by direct interaction of retinoic acid with endothelial cells. Lab Invest 1996;74:476-83
290. Lingen MW, Polverini PJ, Bouck NP. Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma. Cancer Res 1998;58:5551-8
291. West-Mays JA, Sadow PM, Tobin TW, et al. Repair phenotype in corneal fibroblasts is controlled by an interleukin-1 alpha autocritic feedback loop. Invest Ophthalmol Vis Sci 1997;38:1367-79
292. van Setten G, Aspiotis M, Blalock TD, et al. Connective tissue growth factor in pterygium: simultaneous presence with vascular endothelial growth factor - possible contributing factor to conjunctival scarring. Graefes Arch Clin Exp Ophthalmol 2003;241:135-9
293. Maini R, Collison DJ, Maidment JM, et al. Pterygial derived fibroblasts express functionally active histamine and epidermal growth factor receptors. Exp Eye Res 2002;74):237-44
294. Lee SB, Li DQ, Tan DT, et al. Suppression of TGF-beta signaling in both normal conjunctival fibroblasts and pterygial body fibroblasts by amniotic membrane. Curr Eye Res 2000;20:325-34
295. Cao R, Brakenhielm E, Li X, et al. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alphaalpha and -alphabeta receptors. FASEB J 2002;16:1575-83
296. Nakagami T, Murakami A, Okisaka S, Ebihara N. [Pterygium and mast cells--mast cell number, phenotype, and localization of stem cell factor]. Nippon Ganka Gaklzai Zasshi 1997;101:662-8
297. Ren X, Lin YP, Tan DTH, Schultz GS. Elevated expression of TGF-beta and EGF system in pterygia. tissues and matched superior conjunctiva (abstract). Invest Ophthalmol Vis Sci 1998;39(Suppl):S509
298. Sakamoto T, Ueno H, Sonoda K, et al. Blockade of TGF-beta by in vivo gene transfer of a soluble TGF-beta type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis. Gene Ther 2000;7:1915-24
299. Marcovich AL, Morad Y, Sandbank J, et al. Angiogenesis in pterygium: morphometric and immunohistochemical study. Curr Eye Res 2002;25:17-22
300. Gebhardt M, Mentlein R, Schaudig U, et al. Differential expression of vascular endothelial growth factor implies the limbal origin of pterygia. Ophthalmology 2005;112:1023-30
301. Dushku N, John MK, Schultz GS, Reid TW. Pterygia pathogenesis: corneal invasion by matrix metalloprotemase expressing altered limbal epithelial basal cells. Arch Ophthalmol 2001; 119:695-706
302. Naib-Majani W, Eltohami I, Wernert N, et al. Distribution of extracellular matrix proteins in pterygia: an immunohistochemical study. Graefes Arch Clin Exp Ophthalmol 2004;242:332-8
303. Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 2005;333:328-35
304. Erdurmus M, Totan Y. Subconjunctival bevacizumab for corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 2007; 245(10):1577-9
305. Bock F, Onderka J, Dietrich T, et al. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest Ophthalmol Vis Sci 2007;48:2545-52
306. Manzano RP, Peyman GA, Khan P, et al. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol 2007;91:804-7
307. Hosseini H, Nejabat M, Mehryar M, et al. Bevacizumab inhibits corneal neovascularization in an alkali burn induced model of corneal angiogenesis. Clin Experiment Ophthalmol 2007;35:745-8
308. Yoeruek E, Spitzer M, Tatar O, et al., Safety profile of bevacizumab on cultured human corneal cells. Cornea 2007;26:977-82
309. Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 2004; 7:335-45
310. Tanaka T, Kohno H, Yoshitam S, et al. Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res 2001;61:2424-8
311. Stienstra R, Duval C, M 252 Ller M, Kersten S. PPARs, obesity, and inflammation. PPAR Res 2006 Nov 23;2007: 95974 [Epub ahead of print]
312. Azzola A, Havryk A, Chhajed P, et al. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Transplantation 2004;77:275-80
313. Brignole F, Pisella PJ, De Saint Jean M, et al. Flow cytometric analysis of inflammatory markers in KCS: 6-month treatment with topical cyclosporin A. Invest Ophthalmol Vis Sci 2001;42:90-5
314. von Marschall Z, Scholz A, Cramer T, et al. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 2003;95:437-48
315. Wu WZ, Sun HC, Shen YE, et al, Interferon alpha 2a down-regulates VEGF expression through PI3 kinase and MAP kinase signaling pathways. J Cancer Res Clin Oncol 2005;131:169-78
316. Kim MS, Kim YK, Eun HC, et al. All-trans retinoic acid antagonizes UV-induced VEGF production and angiogenesis via the inhibition of ERK activation in human skin keratinocytes. J Invest Dermatol 2006;126:2697-706