炎症因子在圆锥角膜发病机制中的研究进展
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摘要
圆锥角膜(keratoconus,KC)是一种渐进性角膜变薄性疾病,通过角膜膨隆,导致锥状外观,瘢痕形成以及视力下降。各种遗传因素、环境因素(眼摩擦,隐形眼镜磨损,紫外线照射)都与其病因相关。除了遗传和环境因素外,在此过程中炎性发病机制也越来越受到学者重视。本文涵盖了与之最相关和最近发表的关于炎症生物标志物,以进一步阐述圆锥角膜的发病机制,以期为圆锥角膜的治疗提供新思路。
Keratoconus( KC) is a progressive corneal thinning disease which can cause the conical appearance, scar growth and vision loss via corneal ectasia. Various factors were demonstrated to be related to its etiology,including the genetic factors and the environmental factors( i.e. the friction of eyelids and eyeball,the friction of contact lens and eyeball and the UV irradiation). In addition to the genetic and environmental factors, the inflammation cytokines has been reported as another key factor to the pathogenesis of keratoconus, thus received more attention recently. This paper then reviews the recent advances on the effect of inflammation cytokines onpathogenesis of keratoconus. The motivation of this work is to provide important guidance and thoughts for the treatment of keratoconus.
Keratoconus( KC) is a progressive corneal thinning disease which can cause the conical appearance, scar growth and vision loss via corneal ectasia. Various factors were demonstrated to be related to its etiology,including the genetic factors and the environmental factors( i.e. the friction of eyelids and eyeball,the friction of contact lens and eyeball and the UV irradiation). In addition to the genetic and environmental factors, the inflammation cytokines has been reported as another key factor to the pathogenesis of keratoconus, thus received more attention recently. This paper then reviews the recent advances on the effect of inflammation cytokines onpathogenesis of keratoconus. The motivation of this work is to provide important guidance and thoughts for the treatment of keratoconus.
引文
1万奇,邓应平.慢性角膜损伤与圆锥角膜发病机制研究进展.国际眼科杂志2014; 14(8):1410-1412
2 Galvis V, Sherwin T, Tello A, et al. Keratoconus:an inflammatory disorder? Eye(Lond)2015;29(7):843-859
3 Jun AS,Cope L,Speck C, et al. Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients. PLoS One 2011;6(1):e 16437
4 Gordon-Shaag A,Millodot M,Shneor E, et al. The Genetic and Environmental Factors for Keratoconus. Biomed Res Int 2015;2015:795738
5 Khaled ML,Helwa I,Drewry M,et al. Molecular and Histopathological Changes Associated with Keratoconus. Biomed Res Int 2017;2017:7803029
6 Nemet AY,Vinker S, Bahar I,et al. The association of kerato-conus with immune disorders. Cornea 2010; 29(11):1261-1264
7 Balasubramanian SA,Pye DC,Willcox MD. Effects of eye rubbing on the levels of protease,protease activity and cytokines in tears:relevance in keratoconus. Clin Exp Optom 2013; 96(2):214-218
8 Zhou L,Zhao SZ,Koh SK,et al. In-depth analysis of the human tear proteome. J Proteomics 2012;75(13):3877-3885
9 Ubels JL, Schotanus MP, Bardolph SL, et al. Inhibition of UV-B induced apoptosis in corneal epithelial cells by potassium channel modulators. Exp Eye Res 2010;90(2):216-222
10 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(12):2483-2491
11 Cristina KM, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye 2003; 26(3):139-146
12 Fodor M,Kolozsvari BL,Petrovski G,et al. Effect of Contact Lens Wear on the Release of Tear Mediators in Keratoconus. Eye Contact Lens2013;39(2):147-152
13 Nowak DM, Karolak JA,Kubiak J,et al. Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus.Invest Ophthalmol Vis Sci 2013; 54(3):2207-2215
14 Wang Y,Jin T,Zhang X,et al. Common Single Nucleotide P oly morphisms and Keratoconus in the Han Chinese Population.Ophthalmic Genetics 2013; 34(3):160-166
15 Bosnar D, Dekaris I,Gabric N, et al. Influence of interleukin-1 alpha and tumor necrosis factor-alpha production on corneal graft survival. Croat Med J 2006; 47(1):59-66
16 Olofsson EM, Marklund SL, Pedrosa-Domellof F, et al. Interleukin-1 alpha downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells. Mol Vis 2007;13:1285-1290
17 Balasubramanian SA,Pye DC,Willcox MD. Are proteinases the reason for keratoconus? Curr Eye Res 2010;35(3):185-191
18 Moqattash S,Lutton JD. Leukemia Cells and the Cytokine Network:Therapeutic Prospects. Exp Biol Med 2004; 229(2):121-137
19 Shetty R,Deshmukh R, Ghosh A, et al. Altered tear inflammatory profile in Indian keratoconus patients. Indian J Ophthalmol 2017; 65(11):1105-1108
20 Sugaya S, Sakimoto T, Sho JI, et al. Regulation of soluble interleukin-6(IL-6)receptor release from corneal epithelial cells and its role in the ocular surface. Jap J Ophthalmol 2011;55(3):277-282
21 Ebihara N, Matsuda A, Nakamura S, et al. Role of the IL-6Classic-and Trans-Signaling Pathways in Corneal Sterile Inflammation and Wound Healing. Invest Opthalmol Vis Sci 2011; 52(12):8549-8557
22 Balasubramanian SA, Mohan S, Pye D,et al. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmologica 2012;90(4):303-309
23 Li DQ,Lokeshwar BL,Solomon A,et al. Regulation of MMP-9Production by Human Corneal Epithelial Cells. Exp Eye Res 2001; 73(4):449-459
24 Yang YN, Wang F, Zhou W, et al. TNF-αStimulates MMP-2 and MMP-9 Activities in Human Corneal Epithelial Cells via the Activation of FAK/ERK Signaling. Ophthalmic Res 2012;48(4):165-170
25 Du G,Liu C, Li X,et al. Induction of matrix metalloproteinase-1 by tumor necrosis factor-αis mediated by interleukin-6 in cultured fibroblasts of keratoconus. Exp Bio Med 2016;241(18):2033-2041
26 Maertzdorf J,Osterhaus AD,Verjans GM. IL-17 Expression in Human Herpetic Stromal Keratitis:Modulatory Effects on Chemokine Production by Corneal Fibroblasts. J Immunol 2002; 169(10):5897-5903
27 Wojcik KA, Blasiak J,Szaflik J,et al. Role of biochemical factors in the pathogenesis of keratoconus. Acta Biochim Pol 2014; 61(1):55-62
28 Ionescu C, Corbu CG, Tanase C, et al. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus. Disease Markers2016;2016:1243819
29 Sriram S,Robinson P,Pi L,et al. Triple Combination of siRNAs Targeting TGFβ1,TGFβR2,and CTGF Enhances Reduction of Collagen I and Smooth Muscle Actin in Corneal Fibroblasts. Invest Opthalmol Vis Sci 2013:54(13):8214-8223
30 Wilson SE. Corneal myofibroblast biology and pathobiology:Generation,persistence, and transparency. Exp Eye Res 2012; 99:78-88
31 Araki-Sasaki K,Osakabe Y,Fujita K,et al. Collagen fiber changes related to keratoconus with secondary corneal amyloidosis. Int Med Case Rep J 2018;11:193-199
32 Saee-Rad S, Raoofian R, Mahbod M, et al. Analysis of superoxide dismutase 1,dual-specificity phosphatase 1,and transforming growth factor,beta 1 genes expression in keratoconic and non-keratoconic corneas. Mol Vis 2013; 19:2501-2507
33 Karamichos D, Hutcheon AEK, Rich CB, et al. In vitro model suggests oxidative stress involved in keratoconus disease. Sci Rep 2014; 4(1):1-6
34 Priyadarsini S,Hjortdal J,Sarker-Nag A,et al. Gross Cystic Disease Fluid Protein-15/Prolactin-Inducible Protein as a Biomarker for Keratoconus Disease. PLoS One 2014;9(11):e1 13310
35 Engler C,Chakravarti S,Doyle J, et al. Transforming Growth Factor-βSignaling Pathway Activation in Keratoconus. Am J Ophthalmol 2011;151(5):752-759
36 Benito MJ, Calder V, Corrales RM,et al. Effect of TGF-βon ocular surface epithelial cells. Exp Eye Res 2013; 107:88-100
37 Lambiase A,Sacchetti M,Bonini S. Nerve growth factor therapy for corneal disease. Curr Opin Ophthalmol 2012; 23(4):296-302
38 Kolozsvari BL, Petrovski G, Gogolak P, et al. Association between Mediators in the Tear Fluid and the Severity of Keratoconus. Ophthalmic Res 2014; 51(1):46-51
39 Lambiase A,Merlo D,Mollinari C,et al. Molecular basis for keratoconus:Lack of TrkA expression and its transcriptional repression by Sp3. Proc Natl Acad Sci USA 2005; 102(46):16795-16800
2 Galvis V, Sherwin T, Tello A, et al. Keratoconus:an inflammatory disorder? Eye(Lond)2015;29(7):843-859
3 Jun AS,Cope L,Speck C, et al. Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients. PLoS One 2011;6(1):e 16437
4 Gordon-Shaag A,Millodot M,Shneor E, et al. The Genetic and Environmental Factors for Keratoconus. Biomed Res Int 2015;2015:795738
5 Khaled ML,Helwa I,Drewry M,et al. Molecular and Histopathological Changes Associated with Keratoconus. Biomed Res Int 2017;2017:7803029
6 Nemet AY,Vinker S, Bahar I,et al. The association of kerato-conus with immune disorders. Cornea 2010; 29(11):1261-1264
7 Balasubramanian SA,Pye DC,Willcox MD. Effects of eye rubbing on the levels of protease,protease activity and cytokines in tears:relevance in keratoconus. Clin Exp Optom 2013; 96(2):214-218
8 Zhou L,Zhao SZ,Koh SK,et al. In-depth analysis of the human tear proteome. J Proteomics 2012;75(13):3877-3885
9 Ubels JL, Schotanus MP, Bardolph SL, et al. Inhibition of UV-B induced apoptosis in corneal epithelial cells by potassium channel modulators. Exp Eye Res 2010;90(2):216-222
10 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(12):2483-2491
11 Cristina KM, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye 2003; 26(3):139-146
12 Fodor M,Kolozsvari BL,Petrovski G,et al. Effect of Contact Lens Wear on the Release of Tear Mediators in Keratoconus. Eye Contact Lens2013;39(2):147-152
13 Nowak DM, Karolak JA,Kubiak J,et al. Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus.Invest Ophthalmol Vis Sci 2013; 54(3):2207-2215
14 Wang Y,Jin T,Zhang X,et al. Common Single Nucleotide P oly morphisms and Keratoconus in the Han Chinese Population.Ophthalmic Genetics 2013; 34(3):160-166
15 Bosnar D, Dekaris I,Gabric N, et al. Influence of interleukin-1 alpha and tumor necrosis factor-alpha production on corneal graft survival. Croat Med J 2006; 47(1):59-66
16 Olofsson EM, Marklund SL, Pedrosa-Domellof F, et al. Interleukin-1 alpha downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells. Mol Vis 2007;13:1285-1290
17 Balasubramanian SA,Pye DC,Willcox MD. Are proteinases the reason for keratoconus? Curr Eye Res 2010;35(3):185-191
18 Moqattash S,Lutton JD. Leukemia Cells and the Cytokine Network:Therapeutic Prospects. Exp Biol Med 2004; 229(2):121-137
19 Shetty R,Deshmukh R, Ghosh A, et al. Altered tear inflammatory profile in Indian keratoconus patients. Indian J Ophthalmol 2017; 65(11):1105-1108
20 Sugaya S, Sakimoto T, Sho JI, et al. Regulation of soluble interleukin-6(IL-6)receptor release from corneal epithelial cells and its role in the ocular surface. Jap J Ophthalmol 2011;55(3):277-282
21 Ebihara N, Matsuda A, Nakamura S, et al. Role of the IL-6Classic-and Trans-Signaling Pathways in Corneal Sterile Inflammation and Wound Healing. Invest Opthalmol Vis Sci 2011; 52(12):8549-8557
22 Balasubramanian SA, Mohan S, Pye D,et al. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmologica 2012;90(4):303-309
23 Li DQ,Lokeshwar BL,Solomon A,et al. Regulation of MMP-9Production by Human Corneal Epithelial Cells. Exp Eye Res 2001; 73(4):449-459
24 Yang YN, Wang F, Zhou W, et al. TNF-αStimulates MMP-2 and MMP-9 Activities in Human Corneal Epithelial Cells via the Activation of FAK/ERK Signaling. Ophthalmic Res 2012;48(4):165-170
25 Du G,Liu C, Li X,et al. Induction of matrix metalloproteinase-1 by tumor necrosis factor-αis mediated by interleukin-6 in cultured fibroblasts of keratoconus. Exp Bio Med 2016;241(18):2033-2041
26 Maertzdorf J,Osterhaus AD,Verjans GM. IL-17 Expression in Human Herpetic Stromal Keratitis:Modulatory Effects on Chemokine Production by Corneal Fibroblasts. J Immunol 2002; 169(10):5897-5903
27 Wojcik KA, Blasiak J,Szaflik J,et al. Role of biochemical factors in the pathogenesis of keratoconus. Acta Biochim Pol 2014; 61(1):55-62
28 Ionescu C, Corbu CG, Tanase C, et al. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus. Disease Markers2016;2016:1243819
29 Sriram S,Robinson P,Pi L,et al. Triple Combination of siRNAs Targeting TGFβ1,TGFβR2,and CTGF Enhances Reduction of Collagen I and Smooth Muscle Actin in Corneal Fibroblasts. Invest Opthalmol Vis Sci 2013:54(13):8214-8223
30 Wilson SE. Corneal myofibroblast biology and pathobiology:Generation,persistence, and transparency. Exp Eye Res 2012; 99:78-88
31 Araki-Sasaki K,Osakabe Y,Fujita K,et al. Collagen fiber changes related to keratoconus with secondary corneal amyloidosis. Int Med Case Rep J 2018;11:193-199
32 Saee-Rad S, Raoofian R, Mahbod M, et al. Analysis of superoxide dismutase 1,dual-specificity phosphatase 1,and transforming growth factor,beta 1 genes expression in keratoconic and non-keratoconic corneas. Mol Vis 2013; 19:2501-2507
33 Karamichos D, Hutcheon AEK, Rich CB, et al. In vitro model suggests oxidative stress involved in keratoconus disease. Sci Rep 2014; 4(1):1-6
34 Priyadarsini S,Hjortdal J,Sarker-Nag A,et al. Gross Cystic Disease Fluid Protein-15/Prolactin-Inducible Protein as a Biomarker for Keratoconus Disease. PLoS One 2014;9(11):e1 13310
35 Engler C,Chakravarti S,Doyle J, et al. Transforming Growth Factor-βSignaling Pathway Activation in Keratoconus. Am J Ophthalmol 2011;151(5):752-759
36 Benito MJ, Calder V, Corrales RM,et al. Effect of TGF-βon ocular surface epithelial cells. Exp Eye Res 2013; 107:88-100
37 Lambiase A,Sacchetti M,Bonini S. Nerve growth factor therapy for corneal disease. Curr Opin Ophthalmol 2012; 23(4):296-302
38 Kolozsvari BL, Petrovski G, Gogolak P, et al. Association between Mediators in the Tear Fluid and the Severity of Keratoconus. Ophthalmic Res 2014; 51(1):46-51
39 Lambiase A,Merlo D,Mollinari C,et al. Molecular basis for keratoconus:Lack of TrkA expression and its transcriptional repression by Sp3. Proc Natl Acad Sci USA 2005; 102(46):16795-16800