Abstract
The ocular surface is a frequent target tissue of mucosal chronic GVHD (cGVHD). We investigated the histopathological features of the conjunctival microvilli in patients with cGVHD. Conjunctival tissue specimens from patients with cGVHD or Sjögren's syndrome (SS) or from healthy individuals were examined by light microscopy and EM, impression cytology, and immunohistochemistry. The cGVHD conjunctivae showed significantly more metaplasia and fewer goblet cells than the SS and normal conjunctivae. Abundant CD8+ T cells infiltrated the basal epithelia in the cGVHD conjunctiva. The microvilli per standard epithelial unit and the secretory vesicles were counted by analyzing electron micrographs. The mean number of mucosal microvilli was significantly lower in the cGVHD than that in the SS or normal specimens, and the microvilli were significantly shorter, with a smaller height–width ratio. The mean number of secretory vesicles was also significantly lower, and the membrane-spanning mucin thinner, in the cGVHD compared with the SS and normal specimens. Thus, the conjunctival mucosal microvilli of cGVHD patients were significantly different in number and morphology from those of SS and normal subjects. These may be important factors affecting the stability of the tear-film layer and its contribution to cGVHD-related dry eye.
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References
Mancel E, Janin A, Gosset D, Hatron PY, Gosselin B . Conjunctival biopsy in scleroderma and primary Sjogren's syndrome. Am J Ophthalmol 1993; 115: 792–799.
Morroni M, Cangiotti AM, Guarino A, Cinti S . Unusual ultrastructural features in microvillous inclusion disease: a report of two cases. Virchows Arch 2006; 448: 805–810.
Dudek AZ, Mahaseth H, DeFor TE, Weisdorf DJ . Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant 2003; 9: 657–666.
Horwitz ME, Sullivan KM . Chronic graft-versus-host disease. Blood Rev 2006; 20: 15–27.
Ogawa Y, Kuwana M . Dry eye as a major complication associated with chronic graft-versus-host disease after hematopoietic stem cell transplantation. Cornea 2003; 22 (Suppl): S19–S27.
Miljanovic B, Dana R, Sullivan DA, Schaumberg DA . Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol 2007; 143: 409–415.
Robinson MR, Lee SS, Rubin BI, Wayne AS, Pavletic SZ, Bishop MR et al. Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graft-versus-host disease. Bone Marrow Transplant 2004; 33: 1031–1035.
Suzuki M, Usui T, Kinoshita N, Yamagami S, Amano S . A case of sterile corneal perforation after bone marrow transplantation. Eye (Lond) 2007; 21: 114–116.
Ogawa Y, Kuwana M, Yamazaki K, Mashima Y, Yamada M, Mori T et al. Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease. Invest Ophthalmol Vis Sci 2003; 44: 1888–1896.
Ogawa Y, Razzaque MS, Kameyama K, Hasegawa G, Shimmura S, Kawai M et al. Role of heat shock protein 47, a collagen-binding chaperone, in lacrimal gland pathology in patients with cGVHD. Invest Ophthalmol Vis Sci 2007; 48: 1079–1086.
Kamoi M, Ogawa Y, Dogru M, Uchino M, Kawashima M, Goto E et al. Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease. Curr Eye Res 2007; 32: 837–842.
Wang Y, Ogawa Y, Dogru M, Kawai M, Tatematsu Y, Uchino M et al. Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease. Bone Marrow Transplant 2008; 41: 293–302.
Argueso P, Gipson IK . Epithelial mucins of the ocular surface: structure, biosynthesis and function. Exp Eye Res 2001; 73: 281–289.
Gipson IK, Argueso P . Role of mucins in the function of the corneal and conjunctival epithelia. Int Rev Cytol 2003; 231: 1–49.
Spurr-Michaud S, Argueso P, Gipson I . Assay of mucins in human tear fluid. Exp Eye Res 2007; 84: 939–950.
Hori Y, Nishida K, Yamato M, Sugiyama H, Soma T, Inoue T et al. Differential expression of MUC16 in human oral mucosal epithelium and cultivated epithelial sheets. Exp Eye Res 2008; 87: 191–196.
Dilly PN . On the nature and the role of the subsurface vesicles in the outer epithelial cells of the conjunctiva. Br J Ophthalmol 1985; 69: 477–481.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.
Fox RI, Robinson CA, Curd JG, Kozin F, Howell FV . Sjogren's syndrome. Proposed criteria for classification. Arthritis Rheum 1986; 29: 577–585.
Research Subcommittee of the International Dry Eye WorkShop. Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 179–193.
Tsubota K . The importance of the Schirmer test with nasal stimulation. Am J Ophthalmol 1991; 111: 106–108.
Hopwood J . Fixation and fixtative. In: Bancroft JF, Stevens A (eds). Theory and Practive of Histological Techniques, 1996, pp 23–46.
Anderson G GK . Tissue processing, microtomy and paraffin sections. In: Bancroft JD, Stevens A (eds). Theory and Practice of Histological Techniques, 4th edn. 1996 pp 47–68.
Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C et al. The EnVision++ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. J Clin Pathol 1998; 51: 506–511.
Nelson JD, Wright JC . Conjunctival goblet cell densities in ocular surface disease. Arch Ophthalmol 1984; 102: 1049–1051.
Nelson JD . Impression cytology. Cornea 1988; 7: 71–81.
Wang Y, Ogawa Y, Dogru M, Tatematsu Y, Uchino M, Kamoi M et al. Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye. Bone Marrow Transplant 2010; 45: 1077–1083.
Robinson G, Gray T . Electron microscopy, 2: practical procedures: In: Bancroft JD, Stevens A (eds). Theory and Practice of Histological Techniques, 4th edn. Churchill Livingstone: Edinburgh, 1996, pp585–626.
Koufakis DI, Karabatsas CH, Sakkas LI, Alvanou A, Manthos AK, Chatzoulis DZ . Conjunctival surface changes in patients with Sjogren's syndrome: a transmission electron microscopy study. Invest Ophthalmol Vis Sci 2006; 47: 541–544.
Wu K, Jerdeva GV, da Costa SR, Sou E, Schechter JE, Hamm-Alvarez SF . Molecular mechanisms of lacrimal acinar secretory vesicle exocytosis. Exp Eye Res 2006; 83: 84–96.
Prause JU, Jensen OA, Paschides K, Stovhase A, Vangsted P . Conjunctival cell glycoprotein pattern of healthy persons and of patients with primary Sjogren's syndrome—light microscopical investigation using lectin probes. J Autoimmun 1989; 2: 495–500.
Gipson IK . Distribution of mucins at the ocular surface. Exp Eye Res 2004; 78: 379–388.
Danjo Y, Watanabe H, Tisdale AS, George M, Tsumura T, Abelson MB et al. Alteration of mucin in human conjunctival epithelia in dry eye. Invest Ophthalmol Vis Sci 1998; 39: 2602–2609.
Dartt DA . Control of mucin production by ocular surface epithelial cells. Exp Eye Res 2004; 78: 173–185.
Argueso P, Spurr-Michaud S, Russo CL, Tisdale A, Gipson IK . MUC16 mucin is expressed by the human ocular surface epithelia and carries the H185 carbohydrate epitope. Invest Ophthalmol Vis Sci 2003; 44: 2487–2495.
Dogru M, Okada N, Asano-Kato N, Tanaka M, Igarashi A, Takano Y et al. Atopic ocular surface disease: implications on tear function and ocular surface mucins. Cornea 2005; 24 (Suppl): S18–S23.
Jabs DA, Wingard J, Green WR, Farmer ER, Vogelsang G, Saral R . The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease. Arch Ophthalmol 1989; 107: 1343–1348.
Ogawa Y, Shimmura S, Kawakita T, Yoshida S, Kawakami Y, Tsubota K . Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease. Am J Pathol 2009; 175: 2372–2381.
Acknowledgements
We thank Dr Emiko Miki for collecting control samples and Mai Tadaki for her expert technical assistance. This work was supported in part by a grant from the Japanese Ministry of the Education, Science, Sports, and Culture No. 20592058.
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Tatematsu, Y., Ogawa, Y., Shimmura, S. et al. Mucosal microvilli in dry eye patients with chronic GVHD. Bone Marrow Transplant 47, 416–425 (2012). https://doi.org/10.1038/bmt.2011.89
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DOI: https://doi.org/10.1038/bmt.2011.89
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