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Apoptosis in Patients With Posterior Uveitis

Apoptosis in Patients With Posterior Uveitis Abstract Background: Apoptosis plays a part in the pathogenesis of autoimmune diseases. Objective: To investigate the expression of apoptotic markers in the eyes of patients with uveitis. Methods: With the use of immunohistochemical and in situ apoptotic detection techniques, apoptotic molecules (Fas or Fas ligand [FasL]) and nuclear DNA fragmentation were examined in 8 enucleated eyes with Behçet's disease (1), sarcoidosis (1), subretinal fibrosis and uveitis (1), sympathetic ophthalmia (4), and the Vogt-Koyanagi-Harada syndrome (1); in 5 chorioretinal biopsy specimens with acute retinal necrosis (2), multifocal choroiditis (1), sarcoidosis (1), and subretinal fibrosis and uveitis (1); and in 3 normal control eyes. Results: Fas and FasL were constitutively expressed in the normal human retina, but they were expressed much less in the choroid. Increased expression of Fas and FasL was found in the retina, chorioretinal scar, and choroidal granulomas in uveitic eyes. However, Fas and FasL expression was absent in the biopsy specimens with acute retinal necrosis, and little Fas or FasL was noted on infiltrating lymphocytes. DNA fragmentation was also identified in eyes with chorioretinal scar and gliosis. Conclusions: Apoptosis occurs in uveitic eyes and may play a regulatory role in limiting ocular inflammation. In uveitic eyes, a dysregulation of the Fas-FasL apoptotic pathway may lead to gliosis and fibrosis. References 1. Pepose JS, Holland GN, Wilhelmus KR. Ocular Infection & Immunity . St Louis, Mo: Mosby-Year Book Inc; 1996. 2. Nussenblatt RB, Whitcup WM, Palestine AG. Uveitis: Fundamentals and Clinical Practice . 2nd ed. St Louis, Mo: Mosby-Year Book Inc; 1996. 3. Chan CC, Li Q. The immunopathology of uveitis. Br J Ophthalmol. In press. 4. Whitcup SM, Chan CC, Li Q, Nussenblatt RB. Expression of cell adhesion molecules in posterior uveitis . Arch Ophthalmol . 1992;110:662-666.Crossref 5. Chan CC, Detrick B, Nussenblatt RB, Palestine AG, Fujikawa LS, Hooks JJ. HLA-DR antigens on retinal pigment epithelial cells from patients with uveitis . Arch Ophthalmol . 1986;104:725-729.Crossref 6. Cohen J. Apoptosis . Immunol Today . 1993;14:126-130.Crossref 7. Savill J, Fadok V, Henson P, Haslett C. Phagocyte recognition of cells undergoing apoptosis . Immunol Today . 1993;14:131-136.Crossref 8. Carson D, Ribeiro JM. Apoptosis and disease . Lancet . 1993;341:1251-1254.Crossref 9. Nagata S. Fas and Fas ligand: a death factor and its receptor . Adv Immunol . 1994;57:129-144. 10. Nagata S, Golstein P. The Fas death factor . Science . 1995;267:1449-1456.Crossref 11. Lynch DH, Ramsdell F, Alderson MR. Fas and FasL in the homeostatic regulation of immune responses . Immunol Today . 1995;16:569-574.Crossref 12. D'Souza SD, Bonetti B, Balasingam V, et al. Multiple sclerosis: Fas signaling in oligodendrocyte cell death . J Exp Med . 1996;184:2361-2370.Crossref 13. Giordanoc C, Stassi G, Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis . Science . 1997;275:960-964. 14. Griffith TS, Herndon JM, Green DR, Ferguson TA. CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance . Immunity . 1996;5:7-16.Crossref 15. Griffith T, Brunner T, Fletcher S, Green D, Ferguson T. Fas ligand-induced apoptosis as a mechanism of immune privilege . Science . 1995;270:1189-1192.Crossref 16. Chan CC, BenEzra D, Rodrigues MM, et al. Immunohistochemistry and electron microscopy of choroidal infiltrates and Dalen-Fuchs nodules in sympathetic ophthalmia . Ophthalmology . 1985;92:580-590.Crossref 17. Chan CC, Nussenblatt RB, Fujikawa LS, et al. Sympathetic ophthalmia: immunopathological findings . Ophthalmology . 1986;93:690-695.Crossref 18. Chan CC, Wetzig RP, Palestine AG, Kuwabara T, Nussenblatt RB. Immunohistopathology of ocular sarcoidosis . Arch Ophthalmol . 1987;105:1398-1402.Crossref 19. George RK, Chan CC, Whitcup SM, Nussenblatt RB. Ocular immunopathology of Behçet's disease . Surv Ophthalmol . 1997;42:157-162.Crossref 20. Chan C, Palestine A, Kuwabara T, Nussenblatt R. Immunopathologic study of Vogt-Koyanagi-Harada syndrome . Am J Ophthalmol . 1988;105:607-611. 21. Kim MK, Chan CC, Belfort RJ, et al. Histopathologic and immunohistopathologic features of subretinal fibrosis and uveitis syndrome . Am J Ophthalmol . 1987;104:15-23. 22. Martin D, Chan C, de Smet M, et al. The role of chorioretinal biopsy in the management of posterior uveitis . Ophthalmology . 1993;100:705-714.Crossref 23. Chan C, Palestine A, Davis J, et al. Role of chorioretinal biopsy in inflammatory eye disease . Ophthalmology . 1991;98:1281-1286.Crossref 24. Palestine A, Nussenblatt R, Chan C, Hooks J, Friedman L, Kuwabara T. Histopathology of the subretinal fibrosis and uveitis syndrome . Ophthalmology . 1985;92:834-844.Crossref 25. 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.Crossref 26. Suda T, Okazaki T, Naito Y, et al. Expression of the Fas ligand in cells of T cell lineage . J Immunol . 1995;154:3806-3813. 27. Trauth EC, Klas C, Peters AM, et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis . Science . 1989;245:301-305.Crossref 28. Suda T, Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis . J Exp Med . 1994;179:873-879.Crossref 29. Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family . Cell . 1993;75:1169-1178.Crossref 30. Cohen PL, Eisenberg RA. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease . Annu Rev Immunol . 1991;9:243-262.Crossref 31. Berlin J, Armstrong RC, Ottilie S, et al. Death effector domin-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis . Proc Natl Acad Sci U S A . 1997;94:1172-1176.Crossref 32. Liu C-C, Young LHY, Young JD-E. Lymphocyte-mediated cytolysis and disease . N Engl J Med . 1996;335:1651-1659.Crossref 33. Cohen P, Eisenberg P. The Ipr and gld genes in systemic autoimmunity: life and death in the Fas lane . Immunol Today . 1992;13:427-428.Crossref 34. Watanabe-Fukunaga R, Brannon C, Copeland N, Jenkins N, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis . Nature . 1992;356:314-317.Crossref 35. Lynch DH, Watson ML, Alderson MR, et al. The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster . Immunity . 1994;1:131-136.Crossref 36. Aliprantis AO, Diez-Roux G, Mulder LCF, Zychlinsky A, Lang RA. Do macrophages kill through apoptosis? Immunol Today . 1996;17:573-576.Crossref 37. Zembala M, Asherson GL. Human Monocytes . New York, NY: Academic Press Inc; 1989. 38. Gold R, Schmied M, Giegerich G, et al. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques . Lab Invest . 1994;71:219-225. 39. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in progressive crescentic glomerulonephritis . Lab Invest . 1996;74:941-951. 40. Haslett C, Savill JS, Whyte MK, Stern M, Dransfield I, Meagher LC. Granulocyte apoptosis and the control of inflammation . Philos Trans R Soc Lond B Biol Sci . 1994;345:327-333.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1997 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1997.01100160729010
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Abstract

Abstract Background: Apoptosis plays a part in the pathogenesis of autoimmune diseases. Objective: To investigate the expression of apoptotic markers in the eyes of patients with uveitis. Methods: With the use of immunohistochemical and in situ apoptotic detection techniques, apoptotic molecules (Fas or Fas ligand [FasL]) and nuclear DNA fragmentation were examined in 8 enucleated eyes with Behçet's disease (1), sarcoidosis (1), subretinal fibrosis and uveitis (1), sympathetic ophthalmia (4), and the Vogt-Koyanagi-Harada syndrome (1); in 5 chorioretinal biopsy specimens with acute retinal necrosis (2), multifocal choroiditis (1), sarcoidosis (1), and subretinal fibrosis and uveitis (1); and in 3 normal control eyes. Results: Fas and FasL were constitutively expressed in the normal human retina, but they were expressed much less in the choroid. Increased expression of Fas and FasL was found in the retina, chorioretinal scar, and choroidal granulomas in uveitic eyes. However, Fas and FasL expression was absent in the biopsy specimens with acute retinal necrosis, and little Fas or FasL was noted on infiltrating lymphocytes. DNA fragmentation was also identified in eyes with chorioretinal scar and gliosis. Conclusions: Apoptosis occurs in uveitic eyes and may play a regulatory role in limiting ocular inflammation. In uveitic eyes, a dysregulation of the Fas-FasL apoptotic pathway may lead to gliosis and fibrosis. References 1. Pepose JS, Holland GN, Wilhelmus KR. Ocular Infection & Immunity . St Louis, Mo: Mosby-Year Book Inc; 1996. 2. Nussenblatt RB, Whitcup WM, Palestine AG. Uveitis: Fundamentals and Clinical Practice . 2nd ed. St Louis, Mo: Mosby-Year Book Inc; 1996. 3. Chan CC, Li Q. The immunopathology of uveitis. Br J Ophthalmol. In press. 4. Whitcup SM, Chan CC, Li Q, Nussenblatt RB. Expression of cell adhesion molecules in posterior uveitis . Arch Ophthalmol . 1992;110:662-666.Crossref 5. Chan CC, Detrick B, Nussenblatt RB, Palestine AG, Fujikawa LS, Hooks JJ. HLA-DR antigens on retinal pigment epithelial cells from patients with uveitis . Arch Ophthalmol . 1986;104:725-729.Crossref 6. Cohen J. Apoptosis . Immunol Today . 1993;14:126-130.Crossref 7. Savill J, Fadok V, Henson P, Haslett C. Phagocyte recognition of cells undergoing apoptosis . Immunol Today . 1993;14:131-136.Crossref 8. Carson D, Ribeiro JM. Apoptosis and disease . Lancet . 1993;341:1251-1254.Crossref 9. Nagata S. Fas and Fas ligand: a death factor and its receptor . Adv Immunol . 1994;57:129-144. 10. Nagata S, Golstein P. The Fas death factor . Science . 1995;267:1449-1456.Crossref 11. Lynch DH, Ramsdell F, Alderson MR. Fas and FasL in the homeostatic regulation of immune responses . Immunol Today . 1995;16:569-574.Crossref 12. D'Souza SD, Bonetti B, Balasingam V, et al. Multiple sclerosis: Fas signaling in oligodendrocyte cell death . J Exp Med . 1996;184:2361-2370.Crossref 13. Giordanoc C, Stassi G, Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis . Science . 1997;275:960-964. 14. Griffith TS, Herndon JM, Green DR, Ferguson TA. CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance . Immunity . 1996;5:7-16.Crossref 15. Griffith T, Brunner T, Fletcher S, Green D, Ferguson T. Fas ligand-induced apoptosis as a mechanism of immune privilege . Science . 1995;270:1189-1192.Crossref 16. Chan CC, BenEzra D, Rodrigues MM, et al. Immunohistochemistry and electron microscopy of choroidal infiltrates and Dalen-Fuchs nodules in sympathetic ophthalmia . Ophthalmology . 1985;92:580-590.Crossref 17. Chan CC, Nussenblatt RB, Fujikawa LS, et al. Sympathetic ophthalmia: immunopathological findings . Ophthalmology . 1986;93:690-695.Crossref 18. Chan CC, Wetzig RP, Palestine AG, Kuwabara T, Nussenblatt RB. Immunohistopathology of ocular sarcoidosis . Arch Ophthalmol . 1987;105:1398-1402.Crossref 19. George RK, Chan CC, Whitcup SM, Nussenblatt RB. Ocular immunopathology of Behçet's disease . Surv Ophthalmol . 1997;42:157-162.Crossref 20. Chan C, Palestine A, Kuwabara T, Nussenblatt R. Immunopathologic study of Vogt-Koyanagi-Harada syndrome . Am J Ophthalmol . 1988;105:607-611. 21. Kim MK, Chan CC, Belfort RJ, et al. Histopathologic and immunohistopathologic features of subretinal fibrosis and uveitis syndrome . Am J Ophthalmol . 1987;104:15-23. 22. Martin D, Chan C, de Smet M, et al. The role of chorioretinal biopsy in the management of posterior uveitis . Ophthalmology . 1993;100:705-714.Crossref 23. Chan C, Palestine A, Davis J, et al. Role of chorioretinal biopsy in inflammatory eye disease . Ophthalmology . 1991;98:1281-1286.Crossref 24. Palestine A, Nussenblatt R, Chan C, Hooks J, Friedman L, Kuwabara T. Histopathology of the subretinal fibrosis and uveitis syndrome . Ophthalmology . 1985;92:834-844.Crossref 25. 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.Crossref 26. Suda T, Okazaki T, Naito Y, et al. Expression of the Fas ligand in cells of T cell lineage . J Immunol . 1995;154:3806-3813. 27. Trauth EC, Klas C, Peters AM, et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis . Science . 1989;245:301-305.Crossref 28. Suda T, Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis . J Exp Med . 1994;179:873-879.Crossref 29. Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family . Cell . 1993;75:1169-1178.Crossref 30. Cohen PL, Eisenberg RA. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease . Annu Rev Immunol . 1991;9:243-262.Crossref 31. Berlin J, Armstrong RC, Ottilie S, et al. Death effector domin-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis . Proc Natl Acad Sci U S A . 1997;94:1172-1176.Crossref 32. Liu C-C, Young LHY, Young JD-E. Lymphocyte-mediated cytolysis and disease . N Engl J Med . 1996;335:1651-1659.Crossref 33. Cohen P, Eisenberg P. The Ipr and gld genes in systemic autoimmunity: life and death in the Fas lane . Immunol Today . 1992;13:427-428.Crossref 34. Watanabe-Fukunaga R, Brannon C, Copeland N, Jenkins N, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis . Nature . 1992;356:314-317.Crossref 35. Lynch DH, Watson ML, Alderson MR, et al. The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster . Immunity . 1994;1:131-136.Crossref 36. Aliprantis AO, Diez-Roux G, Mulder LCF, Zychlinsky A, Lang RA. Do macrophages kill through apoptosis? Immunol Today . 1996;17:573-576.Crossref 37. Zembala M, Asherson GL. Human Monocytes . New York, NY: Academic Press Inc; 1989. 38. Gold R, Schmied M, Giegerich G, et al. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques . Lab Invest . 1994;71:219-225. 39. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in progressive crescentic glomerulonephritis . Lab Invest . 1996;74:941-951. 40. Haslett C, Savill JS, Whyte MK, Stern M, Dransfield I, Meagher LC. Granulocyte apoptosis and the control of inflammation . Philos Trans R Soc Lond B Biol Sci . 1994;345:327-333.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Dec 1, 1997

References