{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:27:29Z","timestamp":1791844049769,"version":"4.3.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,12,24]],"date-time":"2004-12-24T00:00:00Z","timestamp":1103846400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2004,12,24]],"date-time":"2004-12-24T00:00:00Z","timestamp":1103846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Ophthalmol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Keratocyte loss by apoptosis following epithelial debridement is a well-recognized entity. In a study of corneal buttons obtained from patients of corneal ulcer undergoing therapeutic keratoplasty, we observed loss of keratocytes in the normal appearing corneal stroma, surrounding the zone of inflammation. Based on these observations, we hypothesized that the cell loss in the inflammatory free zone of corneal stroma is by apoptosis that could possibly be a non-specific host response, independent of the nature of infectious agent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To test our hypothesis, in this study, we performed Terminal deoxyribonucleotidyl transferase-mediated d-Uridine 5\" triphosphate Nick End Labelling (TUNEL) staining on 59 corneal buttons from patients diagnosed as bacterial, fungal, viral and\n                      <jats:italic>Acanthamoeba<\/jats:italic>\n                      keratitis. The corneal sections were reviewed for morphologic changes in the epithelium, stroma, type, degree and depth of inflammation, loss of keratocytes in the surrounding stroma (posterior or peripheral). TUNEL positivity was evaluated in the corneal sections, both in the zone of inflammation as well as the surrounding stroma. A correlation was attempted between the keratocyte loss, histologic, microbiologic and clinical features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The corneal tissues were from 59 patients aged between 16 years and 85 years (mean 46 years) and included fungal (22), viral (15), bacterial (14) and\n                      <jats:italic>Acanthamoeba<\/jats:italic>\n                      (8) keratitis. The morphological changes in corneal tissues noted were: epithelial ulceration (52, 88.1%), destruction of Bowman's layer (58, 99%), mild to moderate (28; 47.5%) to severe inflammation (31; 52.5%). Morphologic evidence of disappearance or reduced number of keratocytic nuclei in the corneal stroma was noted in 49 (83%) cases; while the TUNEL positive brown cells were identified in all cases 53\/54 (98%), including cases of fungal (19), bacterial (14), viral (13), and\n                      <jats:italic>Acanthamoeba<\/jats:italic>\n                      keratitis. TUNEL staining was located mostly in the deeper stroma and in few cases the peripheral stroma. TUNEL positivity was also noted with the polymorphonuclear infiltrates and in few epithelial cells (10 of 59, 17%) cases, more with viral infections (6\/10; 60%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We report apoptotic cell death of keratocytes in the corneal stroma in infectious keratitis, a phenomenon independent of type of infectious agent. The inflammatory cells in the zone of inflammation also show evidence of apoptotic cell death. It could be speculated that the infective process possibly triggers keratocyte loss of the surrounding stroma by apoptosis, which could possibly be a protective phenomenon. It also suggests that necrotic cell death and apoptotic cell deaths could occur simultaneously in infective conditions of the cornea.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1471-2415-4-16","type":"journal-article","created":{"date-parts":[[2005,1,12]],"date-time":"2005-01-12T14:28:03Z","timestamp":1105540083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Keratocyte loss in corneal infection through apoptosis: a histologic study of 59 cases"],"prefix":"10.1186","volume":"4","author":[{"given":"Geeta K","family":"Vemuganti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazala","family":"Iftekhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savitri","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2004,12,24]]},"reference":[{"key":"33_CR1","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1016\/S0161-6420(99)90250-6","volume":"106","author":"AI Miedziak","year":"1999","unstructured":"Miedziak AI, Miller MR, Rapuano CJ, Laibson PR, Cohen EJ: Risk factors in microbial keratitis leading to penetrating keratoplasty. Ophthalmology. 1999, 106: 1166-1170. 10.1016\/S0161-6420(99)90250-6.","journal-title":"Ophthalmology"},{"key":"33_CR2","first-page":"157","volume-title":"Ophthalmic Pathology: An Atlas and Textbook","author":"WH Spencer","year":"1996","unstructured":"Spencer WH: Cornea. Ophthalmic Pathology: An Atlas and Textbook. Edited by: Spencer WH. 1996, Philadelphia: W B Saunders, 1: 157-321. 4","edition":"4"},{"key":"33_CR3","first-page":"213","volume":"20","author":"DL Van Horn","year":"1981","unstructured":"Van Horn DL, Davis SD, Hyndiuk RA, Pederson HJ: Experimental Pseudomonas keratitis in the rabbit: bacteriologic, clinical, and microscopic observations. Invest Ophthalmol Vis Sci. 1981, 20: 213-221.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"33_CR4","first-page":"121","volume":"2","author":"PA Thomas","year":"1992","unstructured":"Thomas PA, Geraldine P: Fungal keratitis due to Fusarium and other fungi. J Mycol Med. 1992, 2: 121-131.","journal-title":"J Mycol Med"},{"key":"33_CR5","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1006\/exer.2000.0971","volume":"72","author":"U Gopinathan","year":"2001","unstructured":"Gopinathan U, Ramakrishna T, Millox A, Rao CM, Balasubramaninam D, Kulkarni A, Vemuganti GK, Rao GN: Enzymatic, clinical and histological evaluation of corneal tissues in experimental fungal keratitis in rabbits. Experimental Eye Research. 2001, 72: 433-442. 10.1006\/exer.2000.0971.","journal-title":"Experimental Eye Research"},{"key":"33_CR6","first-page":"42","volume-title":"Corneal surgery \u2013 theory, technique & tissue","author":"ML McDermott","year":"1999","unstructured":"McDermott ML: Stromal wound healing. Corneal surgery \u2013 theory, technique & tissue. Edited by: Brightbill FS. 1999, St Louis: Mosby, 42-48. 3","edition":"3"},{"key":"33_CR7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3928\/1081-597X-19970301-15","volume":"13","author":"SE Wilson","year":"1997","unstructured":"Wilson SE: Molecular cell biology for the refractive corneal surgeon: programmed cell death and wound healing. J Refract Surg. 1997, 13: 171-175.","journal-title":"J Refract Surg"},{"key":"33_CR8","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1097\/00003226-199703000-00013","volume":"16","author":"J Gao","year":"1997","unstructured":"Gao J, Gelber-Schwalb TA, Addeo JV, Stern ME: Apoptosis in the rabbit cornea after photorefractive keratectomy. Cornea. 1997, 16: 200-208.","journal-title":"Cornea"},{"key":"33_CR9","first-page":"276","volume":"39","author":"MC Helena","year":"1998","unstructured":"Helena MC, Baeveldt F, Kim WJ, Wilson SE: Keratocyte apoptosis after corneal surgery. Invest Ophthalmol Vis Sci. 1998, 39: 276-283.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"33_CR10","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s004170000182","volume":"238","author":"Q Li","year":"2000","unstructured":"Li Q, Ashraf MF, Bekoe NA, Stark WJ, Chan CC, O'Brien TP: The role of apoptosis in the early corneal wound healing after excimer laser keratectomy in the rat. Graefes Arch Clin Exp Ophthalmol. 2000, 238: 853-860. 10.1007\/s004170000182.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"33_CR11","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1001\/archopht.119.6.889","volume":"119","author":"SE Wilson","year":"2001","unstructured":"Wilson SE, Mohan RR, Hong JW, Lee JS, Choi R, Mohan RR: The wound healing response after laser in situ keratomileusis and photorefractive keratectomy: elusive control of biological variability and effect on custom laser vision correction. Arch Ophthalmol. 2001, 119: 889-896.","journal-title":"Arch Ophthalmol"},{"key":"33_CR12","first-page":"291","volume":"48","author":"GK Vemuganti","year":"2000","unstructured":"Vemuganti GK, Sharma S, Athmanathan S, Garg P: Keratocyte loss in Acanthamoeba keratitis: phagocytosis, necrosis or apoptosis?. Indian J Ophthalmol. 2000, 48: 291-294.","journal-title":"Indian J Ophthalmol"},{"key":"33_CR13","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/bjc.1972.33","volume":"26","author":"JFR Kerr","year":"1972","unstructured":"Kerr JFR, Wyllie AH, Currie AR: Apoptosis: Basis biological phenomenon with wide range implication in tissue kinetics. Br J Cancer. 1972, 26: 239-257.","journal-title":"Br J Cancer"},{"key":"33_CR14","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1126\/science.7878464","volume":"267","author":"CB Thompson","year":"1995","unstructured":"Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 1995, 267: 1456-1462.","journal-title":"Science"},{"key":"33_CR15","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1007\/BF01920101","volume":"52","author":"A Samali","year":"1996","unstructured":"Samali A, Gorman AM, Cotter TG: Apoptosis \u2013 the story so far. Experientia. 1996, 52: 933-941.","journal-title":"Experientia"},{"key":"33_CR16","first-page":"520","volume":"7","author":"CH Dohlman","year":"1968","unstructured":"Dohlman CH, Gasset AR, Rose J: The effect of the absence of corneal epithelium or endothelium on stromal keratocytes. Invest Ophthalmol. 1968, 7: 520-534.","journal-title":"Invest Ophthalmol"},{"key":"33_CR17","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1001\/archopht.1994.01090140130034","volume":"112","author":"M Campos","year":"1994","unstructured":"Campos M, Szerenyi K, Lee M, McDonnell JM, McDonnell PJ: Keratocyte loss after corneal deepithelialization in primates and rabbits. Arch Ophthalmol. 1994, 112: 254-260.","journal-title":"Arch Ophthalmol"},{"key":"33_CR18","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1006\/exer.1996.0038","volume":"62","author":"SE Wilson","year":"1996","unstructured":"Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M, Chwang EL: 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. 1996, 62: 325-327. 10.1006\/exer.1996.0038.","journal-title":"Exp Eye Res"},{"key":"33_CR19","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1006\/exer.1996.0266","volume":"64","author":"SE Wilson","year":"1997","unstructured":"Wilson SE, Pedroza L, Beuerman R, Hill JM: Herpes simplex virus type-1 infection of corneal epithelial cells induce apoptosis of underlying keratocytes. Exp Eye Res. 1997, 64: 775-779. 10.1006\/exer.1996.0266.","journal-title":"Exp Eye Res"},{"key":"33_CR20","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1080\/152165400410209","volume":"49","author":"VP Skulachev","year":"2000","unstructured":"Skulachev VP: Mitochondria in the Programmed Death Phenomena; A Principle of Biology: \"It Is Better to Die than to be Wrong\". IUBMB Life. 2000, 49: 365-373. 10.1080\/152165400306179.","journal-title":"IUBMB Life"},{"key":"33_CR21","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/S0531-5565(01)00109-7","volume":"36","author":"VP Skulachev","year":"2001","unstructured":"Skulachev VP: The programmed death phenomenon, aging, and the Samurai Law of biology. Experimental Gerontology. 2001, 36: 995-1024. 10.1016\/S0531-5565(01)00109-7.","journal-title":"Experimental Gerontology"},{"key":"33_CR22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0167-5699(89)90231-4","volume":"10","author":"E Martz","year":"1989","unstructured":"Martz E, Howell DM: CTL: Virus control cells first and cytolyic cells second? DNA fragmentation, apoptosis and the prelytic halt hypothesis. Immunol Today. 1989, 10: 79-86. 10.1016\/0167-5699(89)90231-4.","journal-title":"Immunol Today"},{"key":"33_CR23","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/BF02521738","volume":"9","author":"F Franek","year":"1992","unstructured":"Franek F, Vomastek T, Dolnikova J: Fragmented DNA and apoptotic bodies document programmed way of cell death in hybridoma cultures. Cytotechnology. 1992, 9: 117-123.","journal-title":"Cytotechnology"},{"key":"33_CR24","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/path.1711420112","volume":"142","author":"AH Wyllie","year":"1984","unstructured":"Wyllie AH, Morris RG, Smith AL, Dunlop D: Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on acromolecular synthesis. J Pathol. 1984, 142: 67-77.","journal-title":"J Pathol"},{"key":"33_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3260001","volume":"326","author":"GM Cohen","year":"1997","unstructured":"Cohen GM: Caspases: the excecutioners of apoptosis. Biochem J. 1997, 326: 1-16.","journal-title":"Biochem J"},{"key":"33_CR26","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1083\/jcb.119.3.493","volume":"119","author":"Y Gavrieli","year":"1992","unstructured":"Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992, 119: 493-501. 10.1083\/jcb.119.3.493.","journal-title":"J Cell Biol"},{"key":"33_CR27","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1076\/ceyr.16.12.1221.5022","volume":"16","author":"JM Moreau","year":"1997","unstructured":"Moreau JM, Sloop GD, Engel LS, Hill JM, O'Callaghan RJ: Histopathological studies of staphylococcal alpha-toxin: effects on rabbit corneas. Curr Eye Res. 1997, 16: 1221-1228. 10.1076\/ceyr.16.12.1221.5022.","journal-title":"Curr Eye Res"},{"key":"33_CR28","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1136\/bjo.85.5.613","volume":"85","author":"N Ozaki","year":"2001","unstructured":"Ozaki N, Ishizaki M, Ghazizadeh M, Yamanaka N: Apoptosis mediates decrease in cellularity during the regression of Arthus reaction in cornea. Br J Ophthalmol. 2001, 85: 613-618. 10.1136\/bjo.85.5.613.","journal-title":"Br J Ophthalmol"},{"key":"33_CR29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1097\/00003226-199004000-00011","volume":"9","author":"MC Madigan","year":"1990","unstructured":"Madigan MC, Penfold PL, Holden BA, Billson FA: Ultrastructural features of contact lens-induced deep corneal neovascularization and associated stromal leukocytes. Cornea. 1990, 9: 144-151.","journal-title":"Cornea"},{"key":"33_CR30","first-page":"1582","volume":"37","author":"SE Wilson","year":"1996","unstructured":"Wilson SE, Li Q, Weng J, Barry-Lane PA, Jester JV, Liang Q, Wordinger RJ: The Fas-Fas Ligand System and Other Modulators of Apoptosis in the cornea. Invest Ophthalmol Vis Sci. 1996, 37: 1582-1592.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"33_CR31","first-page":"911","volume":"40","author":"KS Cho","year":"1999","unstructured":"Cho KS, Lee EH, Choi JS, et al: Reactive oxygen species induced apoptosis and necrosis in bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 1999, 40: 911-919.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"33_CR32","first-page":"35","volume":"40","author":"WJ Kim","year":"1999","unstructured":"Kim WJ, Helena MC, Mohan RR, Wilson SE: Changes in corneal morphology associated with chronic epithelial injury. Invest Ophthalmol Vis Sci. 1999, 40: 35-42.","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["BMC Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2415-4-16.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2415-4-16\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2415-4-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2415-4-16.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T09:17:10Z","timestamp":1728292630000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcophthalmol.biomedcentral.com\/articles\/10.1186\/1471-2415-4-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,24]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2004,12]]}},"alternative-id":["33"],"URL":"https:\/\/doi.org\/10.1186\/1471-2415-4-16","relation":{},"ISSN":["1471-2415"],"issn-type":[{"value":"1471-2415","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,24]]},"assertion":[{"value":"26 April 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2004","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2004","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"16"}}