Abstract
The most common human disease caused by infection with Toxoplasma gondii is ocular toxoplasmosis, which typically is manifest as recurrent attacks of necrotizing retinal inflammation with subsequent scarring. The multilayered retina contains specialized cell populations, including endothelial cells, epithelial cells, neurons and supporting cells, all of which may be involved in this condition. In vitro investigations of basic mechanisms operating in human ocular toxoplasmosis use cellular and molecular methods that are common to the study of many pathological processes, and the novel aspect of this research is the use of human retinal cell subsets. Most in vivo research on ocular toxoplasmosis is conducted in the laboratory mouse. Experimental models involve local or systemic inoculation of parasites to induce acute disease, or sequential systemic and local parasite inoculations to trigger recurrent disease. We present methods for in vitro and in vivo studies of ocular toxoplasmosis, including dissection of the human eye, and culture and infection of differentiated cell populations from the retina, as well as induction of mouse ocular toxoplasmosis by intraocular, or sequential systemic and intraocular, inoculations, and imaging of toxoplasmic retinal lesions.
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References
Dubey JP (2010) Toxoplasmosis of animals and humans, 2nd edn. CRC Press, Taylor & Francis Group, Boca Raton, FL
London NJ, Hovakimyan A, Cubillan LD et al (2011) Prevalence, clinical characteristics, and causes of vision loss in patients with ocular toxoplasmosis. Eur J Ophthalmol 21:811–819
Holland GN (2004) Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol 137:1–17
Lum F, Jones JL, Holland GN, Liesegang TJ (2005) Survey of ophthalmologists about ocular toxoplasmosis. Am J Ophthalmol 140:724–726
Holland GN (2003) Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. Am J Ophthalmol 136:973–988
Vallochi AL, Muccioli C, Martins MC et al (2005) The genotype of Toxoplasma gondii strains causing ocular toxoplasmosis in humans in Brazil. Am J Ophthalmol 139:350–351
Switaj K, Master A, Borkowski PK et al (2006) Association of ocular toxoplasmosis with type I Toxoplasma gondii strains: direct genotyping from peripheral blood samples. J Clin Microbiol 44:4262–4264
Fekkar A, Ajzenberg D, Bodaghi B et al (2011) Direct genotyping of Toxoplasma gondii in ocular fluid samples from 20 patients with ocular toxoplasmosis: predominance of type II in France. J Clin Microbiol 49:1513–1517
Herrmann DC, Maksimov P, Hotop A et al (2014) Genotyping of samples from German patients with ocular, cerebral and systemic toxoplasmosis reveals a predominance of Toxoplasma gondii type II. Int J Med Microbiol 304:911–916
Barragan A, Sibley LD (2003) Migration of Toxoplasma gondii across biological barriers. Trends Microbiol 11:426–430
Runkle EA, Antonetti DA (2011) The blood-retinal barrier: structure and functional significance. Methods Mol Biol 686:133–148
Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366:1227–1239
Nicholson DH, Wolchok EB (1976) Ocular toxoplasmosis in an adult receiving long-term corticosteroid therapy. Arch Ophthalmol 94:248–254
Yeo JH, Jakobiec FA, Iwamoto T et al (1983) Opportunistic toxoplasmic retinochoroiditis following chemotherapy for systemic lymphoma. A light and electron microscopic study. Ophthalmology 90:885–898
Smith JR, Franc DT, Carter NS et al (2004) Susceptibility of retinal vascular endothelium to infection with Toxoplasma gondii tachyzoites. Invest Ophthalmol Vis Sci 45:1157–1161
Furtado JM, Bharadwaj AS, Ashander LM et al (2012) Migration of Toxoplasma gondii-infected dendritic cells across human retinal vascular endothelium. Invest Ophthalmol Vis Sci 53:6856–6862
Furtado JM, Bharadwaj AS, Chipps TJ (2012) Toxoplasma gondii tachyzoites cross retinal endothelium assisted by intercellular adhesion molecule-1 in vitro. Immunol Cell Biol 90:912–915
Masland RH (2012) The neuronal organization of the retina. Neuron 76:266–280
Vecino E, Rodriguez FD, Ruzafa N et al (2016) Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res 51:1–40
Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85:845–881
Furtado JM, Ashander LM, Mohs K et al (2013) Toxoplasma gondii migration within and infection of human retina. PLoS One 8:e54358
Frenkel JK (1955) Ocular lesions in hamsters; with chronic Toxoplasma and Besnoitia infection. Am J Ophthalmol 39:203–225
Hogan MJ (1951) Ocular toxoplasmosis. Columbia University Press, New York, NY
Nozik RA, O'Connor GR (1968) Experimental toxoplasmic retinochoroiditis. Arch Ophthalmol 79:485–489
Dukaczewska A, Tedesco R, Liesenfeld O (2015) Experimental models of ocular infection with Toxoplasma gondii. Eur J Microbiol Immunol (Bp) 5:293–305
Provis JM, Dubis AM, Maddess T, Carroll J (2013) Adaptation of the central retina for high acuity vision: cones, the fovea and the avascular zone. Prog Retin Eye Res 35:63–81
Culbertson WW, Tabbara KF, O'Connor R (1982) Experimental ocular toxoplasmosis in primates. Arch Ophthalmol 100:321–323
Rochet E, Brunet J, Sabou M et al (2015) Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation. Infect Immun 83:2109–2117
Lu F, Huang S, Hu MS, Kasper LH (2005) Experimental ocular toxoplasmosis in genetically susceptible and resistant mice. Infect Immun 73:5160–5165
Chen J, Qian H, Horai R et al (2013) Use of optical coherence tomography and electroretinography to evaluate retinal pathology in a mouse model of autoimmune uveitis. PLoS One 8:e63904
Wigg JP, Zhang H, Yang D (2015) A quantitative and standardized method for the evaluation of choroidal neovascularization using MICRON III fluorescein angiograms in rats. PLoS One 10:e0128418
Fuma S, Nishinaka A, Inoue Y et al (2017) A pharmacological approach in newly established retinal vein occlusion model. Sci Rep 7:43509
Paques M, Guyomard JL, Simonutti M et al (2007) Panretinal, high-resolution color photography of the mouse fundus. Invest Ophthalmol Vis Sci 48:2769–2774
Xu H, Koch P, Chen M et al (2008) A clinical grading system for retinal inflammation in the chronic model of experimental autoimmune uveoretinitis using digital fundus images. Exp Eye Res 87:319–326
Copland DA, Wertheim MS, Armitage WJ et al (2008) The clinical time-course of experimental autoimmune uveoretinitis using topical endoscopic fundal imaging with histologic and cellular infiltrate correlation. Invest Ophthalmol Vis Sci 49:5458–5465
Chen M, Forrester JV, Xu H (2011) Dysregulation in retinal para-inflammation and age-related retinal degeneration in CCL2 or CCR2 deficient mice. PLoS One 6:e22818
Furtado JM, Davies MH, Choi D et al (2012) Imaging retinal vascular changes in the mouse model of oxygen-induced retinopathy. Transl Vis Sci Technol 1:5
Bharadwaj AS, Appukuttan B, Wilmarth PA et al (2013) Role of the retinal vascular endothelial cell in ocular disease. Prog Retin Eye Res 32:102–180
Blenkinsop TA, Salero E, Stern JH, Temple S (2013) The culture and maintenance of functional retinal pigment epithelial monolayers from adult human eye. Methods Mol Biol 945:45–65
Fernandez-Godino R, Garland DL, Pierce EA (2016) Isolation, culture and characterization of primary mouse RPE cells. Nat Protoc 11:1206–1218
Sonoda S, Spee C, Barron E et al (2009) A protocol for the culture and differentiation of highly polarized human retinal pigment epithelial cells. Nat Protoc 4:662–673
Limb GA, Salt TE, Munro PM et al (2002) In vitro characterization of a spontaneously immortalized human Muller cell line (MIO-M1). Invest Ophthalmol Vis Sci 43:864–869
Gaudin C, Forster V, Sahel J et al (1996) Survival and regeneration of adult human and other mammalian photoreceptors in culture. Invest Ophthalmol Vis Sci 37:2258–2268
Romano C, Hicks D (2007) Adult retinal neuronal cell culture. Prog Retin Eye Res 26:379–397
Lu B, Malcuit C, Wang S et al (2009) Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 27:2126–2135
Khan A, Behnke MS, Dunay IR et al (2009) Phenotypic and gene expression changes among clonal type I strains of Toxoplasma gondii. Eukaryot Cell 8:1828–1836
Roberts CW, Cruickshank SM, Alexander J (1995) Sex-determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production. Infect Immun 63:2549–2555
Mattapallil MJ, Wawrousek EF, Chan CC et al (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53:2921–2927
Lou DA, Hu FN (1987) Specific antigen and organelle expression of a long-term rhesus endothelial cell line. In Vitro Cell Dev Biol 23:75–85
Dunn KC, Aotaki-Keen AE, Putkey FR, Hjelmeland LM (1996) ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res 62:155–169
Ahmado A, Carr AJ, Vugler AA et al (2011) Induction of differentiation by pyruvate and DMEM in the human retinal pigment epithelium cell line ARPE-19. Invest Ophthalmol Vis Sci 52:7148–7159
Samuel W, Jaworski C, Postnikova OA et al (2017) Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells. Mol Vis 23:60–89
Reid TW, Albert DM, Rabson AS et al (1974) Characteristics of an established cell line of retinoblastoma. J Natl Cancer Inst 53:347–360
McFall RC, Sery TW, Makadon M (1977) Characterization of a new continuous cell line derived from a human retinoblastoma. Cancer Res 37:1003–1010
Acknowledgments
This work was supported in part by the Australian Research Council (FT130101648 to JRS) and the National Health and Medical Research Council (GNT1066235 to JRS).
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Smith, J.R., Ashander, L.M., Ma, Y., Rochet, E., Furtado, J.M. (2020). Model Systems for Studying Mechanisms of Ocular Toxoplasmosis. In: Tonkin, C. (eds) Toxoplasma gondii. Methods in Molecular Biology, vol 2071. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9857-9_17
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DOI: https://doi.org/10.1007/978-1-4939-9857-9_17
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