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2014 | 61 | 1 | 55-62
Article title

Role of biochemical factors in the pathogenesis of keratoconus

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Abstracts
EN
Keratoconus (KC) is a corneal disease associated with structural abnormalities in the corneal epithelium, Bowman's layer and stroma and altered concentration of tear components. KC corneas show a different pattern of collagen lamellae than their normal counterparts. Also, a reduction of several collagen types in KC epithelium and stroma was observed. Altered expression and/or activity of lysyl oxidase, a critical enzyme of the biogenesis of connective tissue detected in KC corneas, may weaken covalent bonds between collagen and elastin fibrils, what may lead to biomechanical deterioration of the cornea. Increased activity of matrix metalloproteinases observed in KC may induce the degradation of the extracellular matrix causing damage to the cornea. Oxidative and nitrative stress play an important role in KC pathogenesis and KC corneas are characterized by the disturbed lipid peroxidation and nitric oxide pathways. Malfunctioning of these pathways may lead to accumulation of their toxic by-products inducing several detrimental effects, along with apoptosis of the corneal cells, which may result from the loss of β-actin or increased levels of cytokines, including interleukin-1 and -6. Change in the expression of genes associated with wound healing, including the nerve growth factor and the visual system homeobox 1, may contribute to increased susceptibility of KC corneas to injury. Consequently, biochemical changes may play an important role in KC pathophysiology and, therefore, can be considered in prevention, diagnosis, prognosis and in the therapy of this disease as well.
Year
Volume
61
Issue
1
Pages
55-62
Physical description
Dates
published
2014
received
2013-10-09
revised
2013-12-14
accepted
2014-02-21
(unknown)
2014-03-18
References
  • Abu-Amero KK, Kalantan H, Al-Muammar AM (2011) Analysis of the VSX1 gene in keratoconus patients from Saudi Arabia. Mol Vis 17: 667-672.
  • Ahmadi Hosseini SM, Mohidin N, Abolbashari F, Mohd-Ali B, Santhirathelagan CT (2013) Corneal thickness and volume in subclinical and clinical keratoconus. Int Ophthalmol 33: 139-145.
  • Aldave AJ, Bourla N, Yellore VS, Rayner SA, Khan MA, Salem AK, Sonmez B (2007) Keratoconus is not associated with mutations in COL8A1 and COL8A2. Cornea 26: 963-965.
  • Aoudjehane L, Pissaia A Jr, Scatton O, Podevin P, Massault PP, Chouzenoux S, Soubrane O, Calmus Y, Conti F. (2008) Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway. Lab Invest 88: 973-985.
  • Arnal E, Peris-Martínez C, Menezo JL, Johnsen-Soriano S, Romero FJ (2011) Oxidative stress in keratoconus? Invest Ophthalmol Vis Sci 52: 8592-8597.
  • Balasubramanian SA, Pye DC, Willcox MD (2013) Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus. Clin Exp Optom 96: 214-218.
  • Barbaro V, Di Iorio E, Ferrari S, Bisceglia L, Ruzza A, De Luca M, Pellegrini G (2006) Expression of VSX1 in human corneal keratocytes during differentiation into myofibroblasts in response to wound healing. Invest Ophthalmol Vis Sci 47: 5243-5250.
  • Behndig A, Karlsson K, Johansson BO, Brännström T, Marklund SL (2001) Superoxide dismutase isoenzymes in the normal and diseased human cornea. Invest Ophthalmol Vis Sci 42: 2293-2296.
  • Bureau J, Fabre EJ, Hecquet C, Pouliquen Y, Lorans G (1993) Modification of prostaglandin E2 and collagen synthesis in keratoconus fibroblasts associated with an increase of interleukin-1 alpha receptor number. CR Acad Sci III 316: 425-430.
  • Bhuyan KC, Bhuyan DK (1978) Superoxide dismutase of the eye: relative functions of superoxide dismutase and catalase in protecting the ocular lens from oxidative damage. Biochim Biophys Acta 542: 28-38.
  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5: 9-19.
  • Brown D, Chwa MM, Opbroek A, Kenney MC (1993) Keratoconus corneas: increased gelatinolytic activity appears after modification of inhibitors. Curr Eye Res 12: 571-581.
  • Brown DJ, Lin B, Chwa M, Atilano SR, Kim DW, Kenney MC (2004) Elements of the nitric oxide pathway can degrade TIMP-1 and increase gelatinase activity. Mol Vis 10: 281-288.
  • Burdon KP, Macgregor S, Bykhovskaya Y, Javadiyan S, Li X, Laurie KJ, Muszynska D, Lindsay R, Lechner J, Haritunians T, Henders AK, Dash D, Siscovick D, Anand S, Aldave A, Coster DJ, Szczotka-Flynn L, Mills RA, Iyengar SK, Taylor KD, Phillips T, Montgomery GW, Rotter JI, Hewitt AW, Sharma S, Rabinowitz YS, Willoughby C, Craig JE (2011) Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Invest Ophthalmol Vis Sci 52: 8514-8519.
  • Burdon KP, Vincent AL (2013) Insights into keratoconus from a genetic perspective. Clin Exp Optom 96: 146-154.
  • Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D, Aldave A, Szczotka-Flynn L, Iyengar SK, Taylor KD, Rotter JI, Rabinowitz YS (2012) Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Invest Ophthalmol Vis Sci 53: 4152-4157.
  • Chaerkady R, Shao H, Scott SG, Pandey A, Jun AS, Chakravarti S (2013) The keratoconus corneal proteome: Loss of epithelial integrity and stromal degeneration. J Proteomics 87: 122-131.
  • Cheng EL, Maruyama I, SundarRaj N, Sugar J, Feder RS, Yue BY (2001) Expression of type XII collagen and hemidesmosome-associated proteins in keratoconus corneas. Curr Eye Res 22: 333-340.
  • Chwa M, Atilano SR, Hertzog D, Zheng H, Langberg J, Kim DW, Kenney MC (2008) Hypersensitive response to oxidative stress in keratoconus corneal fibroblasts. Invest Ophthalmol Vis Sci 49: 4361-4369.
  • Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincen (2007) IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta, NF-kappaB, and AP-1 activation. Am J Physiol Heart Circ Physiol 293: H3356-3365.
  • Critchfield JW, Calandra AJ, Nesburn AB, Kenney MC (1988) Keratoconus: I. Biochemical studies. Exp Eye Res 46: 953-963.
  • Dash DP, George S, O'Prey D, Burns D, Nabili S, Donnelly U, Hughes AE, Silvestri G, Jackson J, Frazer D, Héon E, Willoughby CE (2010) Mutational screening of VSX1 in keratoconus patients from the European population. Eye (Lond) 24: 1085-1092.
  • De Bonis P, Laborante A, Pizzicoli C, Stallone R, Barbano R, Longo C, Mazzilli E, Zelante L, Bisceglia L (2011) Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. Mol Vis 17: 2482-2494.
  • Dudakova L, Liskova P, Trojek T, Palos M, Kalasova S, Jirsova K (2012) Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas. Exp Eye Res 104: 74-81.
  • Engler C, Chakravarti S, Doyle J, Eberhart CG, Meng H, Stark WJ, Kelliher C, Jun AS (2011) Transforming growth factor-β signaling pathway activation in Keratoconus. Am J Ophthalmol 151: 752-759.
  • Gajecka M, Radhakrishna U, Winters D, Nath SK, Rydzanicz M, Ratnamala U, Ewing K, Molinari A, Pitarque JA, Lee K, Leal SM, Bejjani BA (2009) Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32. Invest Ophthalmol Vis Sci 50: 1531-1539.
  • Girard MT, Matsubara M, Fini ME (1991) Transforming growth factor-beta and interleukin-1 modulate metalloproteinase expression by corneal stromal cells. Inves Ophthalmol Vis Sci 32: 2441-2454.
  • Gondhowiardjo TD, van Haeringen NJ, Völker-Dieben HJ, Beekhuis HW, Kok JH, van Rij G, Pels L, Kijlstra A (1993) Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. Cornea 12: 146-154.
  • Guan T, Liu C, Ma Z, Ding S (2012) The point mutation and polymorphism in keratoconus candidate gene TGFBI in Chinese population. Gene 503: 137-139.
  • Gukasyan HJ, Kim KJ, Lee VH, Kannan R (2007) Glutathione and its transporters in ocular surface defense. Ocul. Surf 5: 269-279.
  • Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, Willoughby CE (2011) Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am J Hum Genet 89: 628-633.
  • Joseph R, Srivastava OP, Pfister RR (2011) Differential epithelial and stromal protein profiles in keratoconus and normal human corneas. Exp Eye Res 92: 282-298.
  • Joseph R, Srivastava OP, Pfister RR (2012) Downregulation of β-actin gene and human antigen R in human keratoconus. Invest Ophthalmol Vis Sci 53: 4032-4041.
  • Jun AS, Cope L, Speck C, Feng X, Lee S, Meng H, Hamad A, Chakravarti S (2011) Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS One 6: e16437.
  • Kao WW, Vergnes JP, Ebert J, Sundar-Raj CV, Brown SI (1982) Increased collagenase and gelatinase activities in keratoconus. Biochem Biophys Res Commun 107: 929-936.
  • Karakozova M, Kozak M, Wong CC, Bailey AO, Yates JR 3rd, Mogilner A, Zebroski H, Kashina A (2006) Arginylation of β-actin regulates actin cytoskeleton and cell motility. Science 313: 192-196.
  • Karolak JA, Kulinska K, Nowak DM, Pitarque JA, Molinari A, Rydzanicz M, Bejjani BA, Gajecka M (2011) Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus. Mol Vis 17: 827-843.
  • Kenney MC, Brown DJ (2003) The cascade hypothesis of keratoconus. Cont Lens Anterior Eye 26: 139-146.
  • Kenney MC, Chwa M, Atilano SR, Tran A, Carballo M, Saghizadeh M, Vasiliou V, Adachi W, Brown DJ (2005) Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Invest Ophthalmol Vis Sci 46: 823-832.
  • Kenney MC, Chwa M, Opbroek AJ, Brown DJ (1994) Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio. Cornea 13: 114-124.
  • Kim SH, Mok JW, Kim HS, Joo CK (2008) Association of -31T>C and -511 C>T polymorphisms in the interleukin 1 beta (IL1B) promoter in Korean keratoconus patients. Mol Vis 14: 2109-2116.
  • Lambiase A, Merlo D, Mollinari C, Bonini P, Rinaldi AM, D' Amato M, Micera A, Coassin M, Rama P, Bonini S, Garaci E (2005) Molecular basis for keratoconus: lack of TrkA expression and its transcriptional repression by Sp3. Proc Natl Acad Sci USA 102: 16795-16800.
  • Lema I, Sobrino T, Durán JA, Brea D, Díez-Feijoo E (2009) Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol 93: 820-824.
  • Li X, Bykhovskaya Y, Canedo AL, Haritunians T, Siscovick D, Aldave AJ, Szczotka-Flynn L, Iyengar SK, Rotter JI, Taylor KD, Rabinowitz YS (2013) Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. Invest Ophthalmol Vis Sci 54: 2696-2704.
  • Li X, Bykhovskaya Y, Haritunians T, Siscovick D, Aldave A, Szczotka-Flynn L, Iyengar SK, Rotter JI, Taylor KD, Rabinowitz YS (2012) A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. Hum Mol Genet 21: 421-429.
  • Määttä M, Väisänen T, Väisänen MR, Pihlajaniemi T, Tervo T (2006) Altered expression of type XIII collagen in keratoconus and scarred human cornea: Increased expression in scarred cornea is associated with myofibroblast transformation. Cornea 25: 448-453.
  • Marklund SL (1982) Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci USA 79: 7634-7638.
  • Matthews FJ, Cook SD, Majid MA, Dick AD, Smith VA (2007) Changes in the balance of the tissue inhibitor of matrix metalloproteinases (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus. Exp Eye Res 84: 1125-1134.
  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprin (hemocuprein). J Biol Chem 244: 6049-6055.
  • Meek KM (2009) Corneal collagen - its role in maintaining corneal shape and transparency. Biophys Rev 1: 83-93.
  • Meek KM, Tuft SJ, Huang Y, Gill PS, Hayes S, Newton RH, Bron AJ (2005) Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci 46: 1948-1956.
  • Michelacci YM (2003) Collagens and proteoglycans of the corneal extracellular matrix. Braz J Med Biol Res 36: 1037-1946.
  • Mikami T, Meguro A, Teshigawara T, Takeuchi M, Uemoto R, Kawagoe T, Nomura E, Asukata Y, Ishioka M, Iwasaki M, Fukagawa K, Konomi K, Shimazaki J, Nishida T, Mizuki N (2013) Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japan population. Mol Vis 19: 845-851.
  • Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17: 701-738.
  • Nielsen K, Hjortdal J, Pihlmann M, Corydon TJ (2013) Update on the keratoconus genetics. Acta Ophthalmol 91: 106-113.
  • Nowak DM, Karolak JA, Kubiak J, Gut M, Pitarque JA, Molinari A, Bejjani BA, Gajecka M (2013) Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus. Invest Ophthalmol Vis Sci 54: 2207-2215.
  • Olofsson EM, Marklund SL, Pedrosa-Domellöf F, Behndig A (2007) Interleukin-1α downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells. Mol Vis 13: 1285-1290.
  • Poh R, Tan JA, Deva JP, Poo D, Yong Y, Arjunan S (2012) Paraoxonase 1 status in keratoconus: a preliminary study of activity and polymorphism. West Indian Med J 61: 569-573.
  • Qiu Z, Dillen C, Hu J, Verbeke H, Struyf S, Van Damme J, Opdenakker G (2009) Interleukin-17 regulates chemokine and gelatinase B expression in fibroblasts to recruit both neutrophils and monocytes. Immunobiology 214: 835-842.
  • Quantock AJ, Young RD (2008) Development of the corneal stroma, and the collagen-proteoglycan associations that help define its structure and function. Dev Dyn 237: 2607-2621.
  • Rabinowitz YS (1998) Keratoconus. Surv Ophthalmol 42: 297-319.
  • Radner W, Zehetmayer M, Skorpik C, Mallinger R (1998) Altered organization of collagen in the apex of keratoconus corneas. Ophthalmic Res 30: 327-332.
  • Roberg K, Johansson U, Ollinger K (1999) Lysosomal release of cathepsin D precedes relocation of cytochrome c and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress. Free Radic Biol Med 27: 1228-1237.
  • Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS (2010) Keratoconus: a review. Cont Lens Anterior Eye 33: 157-166.
  • Runager K, Basaiawmoit RV, Deva T, Andreasen M, Valnickova Z, Sørensen CS, Karring H, Thøgersen IB, Christiansen G, Underhaug J, Kristensen T, Nielsen NC, Klintworth GK, Otzen DE, Enghild JJ (2011) Human phenotypically distinct TGFBI corneal dystrophies are linked to the stability of the fourth FAS1 domain of TGFBIp. J Biol Chem 286: 4951-4958.
  • Saghizadeh M, Chwa A, Aoki A, Lin B, Pirouzmanesh A, Brown DJ, Ljubimov AV, Kenney MC (2001) Altered expression of growth factors and cytokines in keratoconus, bullous keratophaty and diabetic human corneas. Exp Eye Res 73: 179-189.
  • Saijyothi AV, Fowjana J, Madhumathi S, Rajeshwari M, Thennarasu M, Prema P, Angayarkanni N (2012) Tear fluid small molecular antioxidants profiling shows lowered glutathione in keratoconus. Exp Eye Res 103: 41-46.
  • Sawaguchi S, Twining SS, Yue BY, Chang SH, Zhou X, Loushin G, Sugar J, Feder RS (1994) Alpha 2-macroglobulin levels in normal human and keratoconus corneas. Invest Ophthalmol Vis Sci 35: 4008-4014.
  • Sawaguchi S, Twining SS, Yue BY, Wilson PM, Sugar J, Chan SK (1990) Alpha-1 proteinase inhibitor levels in keratoconus. Exp Eye Res 50: 549-554.
  • Semina EV, Mintz-Hittner HA, Murray JC (2000) Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues. Genomics 63: 289-293.
  • Sherwin T, Brookes NH (2004) Morphological changes in keratoconus: pathology or pathogenesis. Clin Experiment Ophthalmol 32: 211-217.
  • Sherwin T, Brookes NH, Loh IP, Poole CA, Clover GM (2002) Cellular incursion into Bowman's membrane in the peripheral cone of the keratoconic cornea. Exp Eye Res 74: 473-482.
  • Sophos NA, Pappa A, Ziegler TL, Vasiliou V (2001) Aldehyde dehydrogenase gene superfamily: the 2000 update. Chem Biol Interact 132: 323-337.
  • Srivastava OP, Chandrasekaran D, Pfister RR (2006) Molecular changes in selected epithelial proteins in human keratoconus corneas compared to normal corneas. Mol Vis 12: 1615-1525.
  • Stabuc-Silih M, Ravnik-Glavac M, Glavac D, Hawlina M, Strazisar M (2009) Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Mol Vis 15: 2848-2860.
  • Stabuc-Silih M, Strazisar M, Ravnik-Glavac M, Hawlina M, Glavac D (2010) Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol Alp Panonica Adriat 19: 3-10.
  • Udar N, Atilano SR, Brown DJ, Holguin B, Small K, Nesburn AB, Kenney MC (2006) SOD1: a candidate gene for keratoconus. Invest Ophthalmol Vis Sci 47: 3345-3351.
  • Udar N, Kenney MC, Chalukya M, Anderson T, Morales L, Brown D, Nesburn A, Small K (2004) Keratoconus - no association with the transforming growth factor beta-induced gene in a cohort of American patients. Cornea 23: 13-17.
  • Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160: 1-40.
  • Vazirani J, Basu S (2013) Keratoconus: current perspectives. Clin Ophthalmol 7: 2019-2030.
  • Viswanathan D, Males J (2012) Prospective longitudinal study of corneal collagen crosslinking in progressive keratoconus. Clin Experiment Ophthalmol 41: 531-536.
  • Weisiger RA, Fridovich I (1973) Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. J Biol Chem 248: 4793-4796.
  • Wheeler J, Hauser MA, Afshari NA, Allingham RR, Liu Y (2012) The genetics of keratoconus: a review. Reprod Syst Sex Disord (Suppl 6): pii: 001.
  • Wilson SE, He YG, Lloyd SA (1992) EGF, EGF receptor, basic FGF, TGF beta-1, and interleukin-1 alpha mRNA in human corneal epithelial cells and stromal fibroblasts. Invest Ophthalmol Vis Sci 33: 1756-1765.
  • Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M, Chwang EL (1996) Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing. Exp Eye Res 62: 325-327.
  • Wise R, Wilson SE, He YG, Weng J (1994) Interleukin-1 alpha induces apoptosis in human corneal stromal fibroblast cells. Invest Ophthalmol Vis Sci 35: 1980.
  • Wojcik KA, Kaminska A, Blasiak J, Szaflik J, Szaflik JP (2013) Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy. Int J Mol Sci 14: 19294-19308.
  • Zhao M, Antunes F, Eaton JW, Brunk UT (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270: 3778-3786.
  • Zhou L, Sawaguchi S, Twining SS, Sugar J, Feder RS, Yue BY (1998) Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Invest Ophthalmol Vis Sci 39: 1117-1124.
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