Abstract
Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature, the presence of mononuclear inflammatory infiltrate (MNII) and parasites in the vasculature of choroids in infected eyes. No inflammatory infiltrate was observed; RPE cells were identified near the MNII in nuclear and plexiforme layers. RPE cells were also found on the ganglion cell layer and in the outer segments of the photoreceptor. The morphology showed that RPE cells caused a discontinuity in the nuclear and plexiforme layers. Clusters of parasites were found surrounded by RPE cells and MNII in the inner plexiforme layers. Ultrastructural analysis showed that RPE cells migrated through the epithelium into the inner retinal layers. We did not observe Toxoplasma cysts in many eyes in which pathological changes were detected. Only 8.3% of the animals had Toxoplasma cysts in the inner nuclear layer in the absence of inflammatory cells. The migration of RPE cells can be triggered by a disruption of the RPE monolayer or injury to the neural retina, as in the case of toxoplasmosis.
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References
Berengo A, Frezzotti R (1962) Active neuro-ophthalmic toxoplasmosis ophthalmic. Ophthalmology 89:1299–1302
Bok D, Young R (1979) Phagocytic properties of the retinal pigment epithelium. In: Zinn KM, Marmar MF (eds) The retinal pigment epithelium. Harvard University Press, Cambridge
Camargo ME, Leser PG, Leser WSP (1976) Diagnostic information from serological tests in human toxoplasmosis. Rev Inst Med Trop São Paulo 18:215–226
Crafoord S, Dafgard Koop E, Seregard S, Algvere PV (2000) Cellular migration into neural retina following implantation of melanin granules in the subretinal space. Graefes Arch Clin Exp Ophthalmol 238:682–689
Forbes MS, Plantholt BA, Sperelakis N (1977) Cytochemical staining procedures selective for sarcotubular systems of muscle: modification and applications. J Ultrastruct Res 60:306–327
Freyre A (1995) Separation of toxoplasma cysts from brain tissue and liberation of viable bradyzoites. J Parasitol 81:1008–1010
Gaspari A, Jenkins MK, Katz S (1988) Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones. J Immunol 141:2216–2220
Gazzinelli RT, Brézin A, Li Qian, Nussenblatt RB, Chan CC (1994) Toxoplasma gondii: acquired ocular toxoplasmosis in the murine model, protective role of TNF-α and IFN-γ. Exp Parasitol. 78:217–229
Han QH, Hui YN, Du HJ, Zhang WJ, Ma JX, Wang SY (2001) Migration of retinal pigment epithelial cells in vitro modulated by monocyte chemotactic protein-1: enhancement and inihibition. Graefes Arch Clin Exp Ophthalmol 239:531–538
Hepler PK (1981) The structure of the endoplasmic reticulum by osmium tetroxide-potassium ferricyanide staining. Eur J Cell Biol 26:102–110
Johnson DA, Fields C, Fallon A, Fitzgerald ME, Viar MJ, Johnson LR (2002) Polymine-depedent migration of retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 43:1228–1233
Liversidge J, McKay D, Mullen G, Forrester JV (1993) Retinal pigment epithelial cells modulate lymphocyte function at the blood-retina barrier by autocrine PGE2 and membrane-bound mechanisms. Cell Immunol 149:315–330
Popiel I, Gold MC, Booth KS (1996) Quantification of Toxoplasma gondii bradyzoites. J Parasitol 82:330–332
Remington JS, Desmonts G (1976) Toxoplasmosis. In: Remington JS, Klein JO (eds) Infections diseases of the fetus and newborn infant. Saunders, Philadelphia, pp 191–332
Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212
Streilein JM (1969) Peripheral tolerance induction: lessons from immune privileged sites and tissue. Transplant Proc 28:2066–2070
Vallochi Al, Nkamura MV, Schlesinger D, Martins MC, Silveira C, Belfort RJr, Rizzo LV. (2002) Ocular toxoplasmosis: more than just meets the eye. Scand J Immunol 55:324–328
Wenkel H, Streilein JW (1998) Analysis of immune deviation elicited by antigens injected into the subretinal space. Invest Ophthalmol Vis Sci 39:1823–1834
Willermain F, Casper-Velu L, Nowak B, Stordeur P, Mosselmans R, Salmon I, Velu T, Bruyns C (2002) Retinal pigment epithelial cells phagocytosis of T lymphocytes: possible implication in the immune privilege of the eye. Br J Ophthalmol 86:1417–1421
Acknowledgements
The authors thank Dr. Fabio Santori for the English revision, Dr. Helene Santos Barbosa for suggestions and Mr. Genézio Lopes de Faria for part of the technical support. This work was supported by grant from Instituto Oswaldo Cruz.
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Tedesco, R.C., Smith, R.L., Corte-Real, S. et al. Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection. Parasitol Res 92, 467–472 (2004). https://doi.org/10.1007/s00436-003-1031-2
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DOI: https://doi.org/10.1007/s00436-003-1031-2