Experimental autoimmune uveoretinitis initiated by non-phagocytic destruction of inner segments of photoreceptor cells by Mac-1(+) mononuclear cells.
EAU in mice is a model of human posterior uveitis. EAU is a Th1-dependent disease that has been assumed to target the neural retina and related tissues; however, in situ effector cells and the target have not yet been clearly demonstrated. In the present study, we induced EAU in B10R mice by immunizing them with human interphotoreceptor retinoid-binding protein peptide 161-180. Histological examinations revealed that EAU occurred approximately 11 days after the immunization and reached a peak on day 14. Retinae from normal or EAU mice were treated with proteases to obtain mono-dispersed cells. The mono-dispersed cells thus obtained were separated into three to four fractions by discontinuous Percoll density-gradient (e.g. PBS/40/60) centrifugation. In normal mice, 94% of the total cells were recovered in two fractions (i.e. PBS/40 and pellet); and these fractions mainly contained inner and outer segments and cell bodies of photoreceptor cells and RPE cells, respectively. In EAU mice, additional cells (i.e. inflammatory cells) were obtained at the 40/60 interface. Electron microscopic examination showed that tissue damage during EAU was initiated by non-phagocytic destruction of inner segments by Mac-1(+) mononuclear cells on day 11, followed by phagocytic activity of macrophages against outer segments and RPE cells on day 14. In vitro culturing of normal retinal cells with EAU infiltrates suggested the involvement of TNF-alpha and NO in the tissue damage. These results indicate that EAU was initiated by non-phagocytic destruction of inner segments of photoreceptor cells by Mac-1(+) mononuclear cells.
Miura-Takeda
Sayako
S
Department of Physiology, Osaka Medical College, Takatsuki, Osaka, Japan.
Tashiro-Yamaji
Junko
J
Oku
Hidehiro
H
Takahashi
Takeshi
T
Shimizu
Tetsunosuke
T
Sugiyama
Tetsuya
T
Ikeda
Tsunehiko
T
Kubota
Takahiro
T
Yoshida
Ryotaro
R
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D055355:Opsins / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis; D055211:Retinal Photoreceptor Cell Inner Segment / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D015866:Uveitis, Posterior / Q000235:genetics / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D016177:Macrophage-1 Antigen; D055355:Opsins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial