Increased Corneal Epithelial Turnover Contributes to Abnormal Homeostasis in the Pax6+/- Mouse Model of Aniridia

PLoS ONE

Volumn 8, Issue 8, 2013, Pages

  Douvaras, Panagiotis ^a,d   Mort, Richard L ^a,c   Edwards, Dominic ^a   Ramaesh, Kanna ^b   Dhillon, Baljean ^a   Morley, Steven D ^a   Hill, Robert E ^c   West, John D ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b GARTNAVEL GENERAL HOSPITAL   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d New York Stem Cell Foundation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BROXURIDINE; CD31 ANTIGEN; TRANSCRIPTION FACTOR PAX6;

AGE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANIRIDIA; ARTICLE; CELL COUNT; CELL DIFFERENTIATION; CELL LABELING; CELL METABOLISM; CORNEA EPITHELIUM; CORNEAL ENDOTHELIAL CELL LOSS; FEMALE; HETEROZYGOTE; MALE; MOUSE; NONHUMAN; PROTEIN METABOLISM; WILD TYPE;

ANIMALS; ANIRIDIA; CELL MOVEMENT; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; EPITHELIUM, CORNEAL; EYE PROTEINS; FEMALE; GENOTYPE; HOMEODOMAIN PROTEINS; HOMEOSTASIS; LIMBUS CORNEAE; MALE; MICE; MICE, KNOCKOUT; MOSAICISM; PAIRED BOX TRANSCRIPTION FACTORS; REPRESSOR PROTEINS; STEM CELLS;

EID: 84881505750     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0071117     Document Type: Article

References (82)

1. Davanger M, Evensen A, (1971) Role of the pericorneal papillary structure in renewal of corneal epithelium. Nature 229: 560-561.
2. Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM, (1989) Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57: 201-209.
3. Kinoshita S, Friend J, Thoft RA, (1981) Sex chromatin of donor corneal epithelium in rabbits. Invest Ophthalmol Vis Sci 21: 434-441.
4. Buck RC, (1985) Measurement of centripetal migration of normal corneal epithelial cells in the mouse. Invest Ophthalmol Vis Sci 26: 1296-1299.
5. Nagasaki T, Zhao J, (2003) Centripetal movement of corneal epithelial cells in the normal adult mouse. Invest Ophthalmol Vis Sci 44: 558-566.
6. Lehrer MS, Sun TT, Lavker RM, (1998) Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation. J Cell Sci 111: 2867-2875.
7. Beebe DC, Masters BR, (1996) Cell lineage and the differentiation of corneal epithelial cells. Invest Ophthalmol Vis Sci 37: 1815-1825.
8. Potten CS, Morris RJ (1988) Epithelial stem cells in vivo. J Cell Sci: 45-62.
9. Pajoohesh-Ganji A, Pal-Ghosh S, Simmens SJ, Stepp MA, (2006) Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse. Stem Cells 24: 1075-1086.
10. Zhao J, Mo V, Nagasaki T, (2009) Distribution of label-retaining cells in the limbal epithelium of a mouse eye. J Histochem Cytochem 57: 177-185.
11. Wei ZG, Cotsarelis G, Sun TT, Lavker RM, (1995) Label-retaining cells are preferentially located in fornical epithelium- implications on conjunctival epithelial homeostasis. Invest Ophthalmol Vis Sci 36: 236-246.
12. Chen WS, Ishikawa M, Yamaki K, Sakuragi S, (2003) Wistar rat palpebral conjunctiva contains more slow-cycling stem cells that have larger proliferative capacity: Implication for conjunctival epithelial homeostasis. Jap J Ophthalmol 47: 119-128.
13. Nagasaki T, Zhao J, (2005) Uniform distribution of epithelial stem cells in the bulbar conjunctiva. Invest Ophthalmol Vis Sci 46: 126-132.
14. Hanson IM, Seawright A, Hardman K, Hodgson S, Zaletayev D, et al. (1993) PAX6 mutations in aniridia. Hum Mol Genet 2: 915-920.
15. Martha A, Ferrell RE, Mintzhittner H, Lyons LA, Saunders GF, (1994) Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins. Am J Hum Genet 54: 801-811.
16. Ton CCT, Hirvonen H, Miwa H, Weil MM, Monaghan P, et al. (1991) Positional cloning and characterization of a paired box-containing and homeobox-containing gene from the aniridia region. Cell 67: 1059-1074.
17. Vincent MC, Pujo AL, Olivier D, Calvas P, (2003) Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. Eur J Hum Genet 11: 163-169.
18. Mackman G, Brightbill F, Optiz J, (1979) Corneal changes in aniridia. Am J Ophthalmol 8: 497-502.
19. Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L, (1984) Aniridia- a review. Surv Ophthalmol 28: 621-642.
20. Nishida K, Kinoshita S, Ohashi Y, Kuwayama Y, Yamamoto S, (1995) Ocular surface abnormalities in aniridia. Am J Ophthalmol 120: 368-375.
21. Ramaesh T, Collinson JM, Ramaesh K, Kaufman MH, West JD, et al. (2003) Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy. Invest Ophthalmol Vis Sci 44: 1871-1878.
22. Collinson JM, Chanas SA, Hill RE, West JD, (2004) Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6+/- mouse Invest Ophthalmol Vis Sci. 45: 1101-1108.
23. Puangsricharern V, Tseng SCG, (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102: 1476-1485.
24. Collinson JM, Morris L, Reid AI, Ramaesh T, Keighren MA, et al. (2002) Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium. Dev Dyn 224: 432-440.
25. Mort RL, Ramaesh T, Kleinjan DA, Morley SD, West JD, (2009) Mosaic analysis of stem cell function and wound healing in the mouse corneal epithelium. BMC Dev Biol 9: 4.
26. Douvaras P, Webb S, Whitaker DA, Dorà N, Hill RE, et al. (2012) Rare corneal clones in mice suggest an age-related decrease of stem cell activity and support the limbal epithelial stem cell hypothesis. Stem Cell Res 8: 109-119.
27. Davis J, Duncan MK, Robison WG, Piatigorsky J, (2003) Requirement for Pax6 in corneal morphogenesis: a role in adhesion. J Cell Sci 116: 2157-2167.
28. Ramaesh T, Ramaesh K, Collinson JM, Chanas SA, Dhillon B, et al. (2005) Developmental and cellular factors underlying corneal epithelial dysgenesis in the Pax6+/- mouse model of aniridia. Exp Eye Res 81: 224-235.
29. Ou JX, Lowes C, Collinson JM, (2010) Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal epithelia. Invest Ophthalmol Vis Sci 51: 1415-1423.
30. Liu CY, Zhu G, Westerhausenlarson A, Converse R, Kao CWC, et al. (1993) Cornea-specific expression of K12 keratin during mouse development. Curr Eye Res 12: 963-974.
31. Shiraishi A, Converse RL, Liu CY, Zhou F, Kao CWC, et al. (1998) Identification of the cornea-specific keratin 12 promoter by in vivo particle-mediated gene transfer. Invest Ophthalmol Vis Sci 39: 2554-2561.
32. Liu JJ, Kao WWY, Wilson SE, (1999) Corneal epithelium-specific mouse keratin K12 promoter. Exp Eye Rese 68: 295-301.
33. Kao WWY, Liu CY, Converse RL, Shiraishi A, Kao CWC, et al. (1996) Keratin 12-deficient mice have fragile corneal epithelia. Invest Ophthalmol Vis Sci 37: 2572-2584.
34. Ou J, Walczysko P, Kucerova R, Rajnicek AM, McCaig CD, et al. (2008) Chronic wound state exacerbated by oxidative stress in Pax6+/- aniridia-related keratopathy. J Pathol 215: 421-430.
35. Quinn JC, West JD, Hill RE, (1996) Multiple functions for Pax6 in mouse eye and nasal development. Genes Dev 10: 435-446.
36. Tan S-S, Williams EA, Tam PPL, (1993) X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nat Genet 3: 170-174.
37. Mort RL, Bentley AJ, Martin FL, Collinson JM, Douvaras P, et al. (2011) Effects of aberrant Pax6 gene dosage on mouse corneal pathophysiology and corneal epithelial homeostasis PLoS One. 6: e28895.
38. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider N, (1990) Effects of intermittent feeding upon body-weight and life-span in inbred mice: Interaction of genotype and age. Mech Ageing Develop 55: 69-87.
39. Pal-Ghosh S, Pajoohesh-Ganji A, Brown M, Stepp MA, (2004) A mouse model for the study of recurrent corneal epithelial erosions: α9β1 integrin implicated in progression of the disease. Invest Ophthalmol Vis Sci 45: 1775-1788.
40. Mort RL, (2009) Quantitative analysis of patch patterns in mosaic tissues with ClonalTools software. J Anat 215: 698-704.
41. Roach SA (1968) The Theory of Random Clumping. London: Methuen. 94 p.
42. West JD, (1976) Clonal development of the retinal epithelium in mouse chimaeras and X-inactivation mosaics. J Embryol Exp Morphol 35: 445-461.
43. Hodson BA, Unbekandt M, Keighren MA, Springbett A, West JD, (2011) Evaluation of methods for one-dimensional spatial analysis of two-dimensional patterns in mouse chimaeras. J Anat 219: 418-437.
44. West JD, Hodson BA, Keighren MA, (1997) Quantitative and spatial information on the composition of chimaeric fetal mouse eyes from single histological sections. Develop Growth Differ 39: 305-317.
45. Schmidt GH, Wilkinson MM, Ponder BAJ, (1986) Non-random spatial arrangement of clone sizes in chimaeric retinal pigment epithelium. J Embryol Exp Morph 91: 197-208.
46. Yoshida S, Shimmura S, Kawakita T, Miyashita H, Den S, et al. (2006) Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces. Invest Ophthalmol Vis Sci 47: 4780-4786.
47. Pajoohesh-Ganji A, Ghosh SP, Stepp MA, (2004) Regional distribution of α9β1 integrin within the limbus of the mouse ocular surface. Dev Dyn 230: 518-528.
48. Pajoohesh-Ganji A, Stepp MA, (2005) In search of markers for the stem cells of the corneal epithelium. Biol Cell 97: 265-276.
49. Hanna C, O'Brien JE, (1960) Cell production and migration in the epithelial layer of the cornea. Arch Ophthal 64: 536-539.
50. Cenedella RJ, Fleschner CR, (1990) Kinetics of corneal epithelium turnover in vivo- Studies of Lovastatin. Invest Ophthalmol Vis Sci 31: 1957-1962.
51. Haskjold E, Bjerknes R, Bjerknes E, (1989) Migration of cells in the rat corneal epithelium. Acta Ophthalmologica 67: 91-96.
52. Sharma A, Coles WH, (1989) Kinetics of corneal epithelial maintenence and graft loss- A population balance model Invest Ophthal Vis Sci. 30: 1962-1971.
53. Haddad A, (2000) Renewal of the rabbit corneal epithelium as investigated by autoradiography after intravitreal injection of 3H-thymidine. Cornea 19: 378-383.
54. Kaufmann B, Gay H, Hollaender A, (1944) Distribution of mitoses in the corneal epithelium of the rabbit and the rat. Anat Rec 90: 161-178.
55. Haskjold E, Refsum SB, Bjerknes R, (1990) Circadian variations in the DNA synthesis of the rat corneal epithelium- A study using double labelling with tritiated thymidine. Virchows Arch B Cell Pathol 58: 229-234.
56. Lavker RM, Dong G, Cheng SZ, Kudoh K, Cotsarelis G, et al. (1991) Relative proliferative rates of limbal and corneal epithelia- Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-synthesizing keratinocytes. Invest Ophthalmol Vis Sci 32: 1864-1875.
57. Szerenyi K, Wang XW, Gabrielian K, Labree L, McDonnell PJ, (1994) Immunochemistry with 5-bromo-2-deoxyuridine for visualization of mitotic cells in the corneal epithelium. Cornea 13: 487-492.
58. Scheving LE, Pauly JE, (1967) Circadian phase relationships of thymidine-3H uptake, labeled nuclei, grain counts and cell division rate in rat corneal epithelium. J Cell Biol 32: 677-683.
59. Li LH, Clevers H, (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327: 542-545.
60. Snippert HJ, Clevers H, (2011) Tracking adult stem cells. EMBO Rep 12: 113-122.
61. Buczacki SJA, Zecchini HI, Nicholson AM, Russell R, Vermeulen L, et al. (2013) Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 495: 65-69.
62. Nakagawa T, Nabeshima YI, Yoshida S, (2007) Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Dev Cell 12: 195-206.
63. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, et al. (2010) Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143: 134-144.
64. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ, (2010) Intestinal stem cell replacement follows a pattern of neutral drift. Science 330: 822-825.
65. Klein AM, Simons BD, (2011) Universal patterns of stem cell fate in cycling adult tissues. Development 138: 3103-3111.
66. Mort RL, Douvaras P, Morley SD, Dorà N, Hill RE, et al. (2012) Stem cells and corneal epithelial maintenance: Insights from the mouse and other animal models. In: Kubiak JZ, editor. Results Probl Cell Differ, 55, "Mouse Development: From Oocyte to Stem Cells". Berlin & Heidelberg: Springer-Verlag. 357-394.
67. Zhang W, Zhao J, Chen L, Urbanowicz MM, Nagasaki T, (2008) Abnormal epithelial homeostasis in the cornea of mice with a destrin deletion. Mol Vis 14: 1929-1939.
68. Ramaesh T, Ramaesh K, Leask R, Springbett A, Riley SC, et al. (2006) Increased apoptosis and abnormal wound-healing responses in the heterozygous Pax6+/- mouse cornea. Invest Ophthalmol Vis Sci 47: 1911-1917.
69. Kucerova R, Ou JX, Lawson D, Leiper LJ, Collinson JM, (2006) Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6+/- mouse model of aniridia-related keratopathy. Invest Ophthal Vis Sci 47: 5276-5282.
70. Majo F, Rochat A, Nicolas M, Jaoude GA, Barrandon Y, (2008) Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature 456: 250-255.
71. Chan RWS, Gargett CE, (2006) Identification of label-retaining cells in mouse endometrium. Stem Cells 24: 1529-1538.
72. Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ, (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121: 1109-1121.
73. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, et al. (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304: 1338-1340.
74. Shi S, Gronthos S, (2003) Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Min Res 18: 696-704.
75. Staszkiewicz J, Gimble J, Cain C, Dietrich M, Burk D, et al. (2009) Flow cytometric and immunohistochemical detection of in vivo BrdU-labeled cells in mouse fat depots. Biochem Biophys Res Com 378: 539-544.
76. Pawelczyk E, Arbab AS, Chaudhry A, Balakumaran A, Robey PG, et al. (2008) In vitro model of bromodeoxyuridine or iron oxide nanoparticle uptake by activated macrophages from labeled stem cells: Implications for cellular therapy. Stem Cells 26: 1366-1375.
77. Pawelczyk E, Jordan EK, Balakumaran A, Chaudhry A, Gormley N, et al. (2009) In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages. PLoS One 4 e6712.
78. Pajoohesh-Ganji A, Pal-Ghosh S, Tadvalkar G, Stepp MA, (2012) Corneal goblet cells and their niche: Implications for corneal stem cell deficiency. Stem Cells 30: 2032-2043.
79. Marinari E, Mehonic A, Curran S, Gale J, Duke T, et al. (2012) Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature 484: 542-546.
80. Thoft RA, Friend J, (1983) The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci 24: 1442-1443.
81. Li W, Chen YT, Hayashida Y, Blanco G, Kheirkah A, et al. (2008) Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases. J Pathol 214: 114-122.
82. Lee H, Khan R, O'Keefe M, (2008) Aniridia: current pathology and management. Acta Ophthalmologica 86: 708-715.