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Journal Français d'Ophtalmologie
Volume 35, n° 4
pages 251-259 (avril 2012)
Doi : 10.1016/j.jfo.2011.05.003
Received : 10 Mars 2011 ;  accepted : 13 May 2011
Early involvement of nitric oxide in mechanisms of pathogenesis of experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein (IRBP)
Implication précoce du monoxyde d’azote dans les mécanismes de pathogenèse au cours de l’uvéite auto-immune expérimentale induite par l’IRBP
 

Figure 1




Figure 1 : 

Histological disorders observed on retinas of interphotoreceptor matrix extract (IPMe) and interphotoreceptor retinoid binding protein (IRBP)-immunized Wistar rats. (A) Light microscopy image of histological section from a control retina showing the typical stratiform morphology and the ordered retina layers. (B), (C) & (D) Histological retinal sections of IPMe-immunized Wistar rats, respectively on day 7, 14 and 21 after immunization. Normal retina morphology is seen on day 7 post immunization, while on day 14, a complete retina structure disruption is noted with retina folding and the presence of granuloma (yellow arrow). On day 21 after immunization, retina architecture disruption is still noted with severe photoreceptor degeneration (red arrow). (E), (F) & (G) Histological retinal sections of IRBP-immunized Wistar rats, respectively on day 7, 14 and 21 after immunization. Normal retina morphology is seen on both days 7 and 14 post immunization. On day 21, we notice a great architecture disruption with photoreceptor degeneration and damage affecting all retina layers. All images were taken of 5μm sections from the posterior segment of Wistar rat eyes stained with haematoxylin eosin, magnification×400. V: vitreous; GCL: ganglion cell layer; IPL: inner plexiform layer; OPL: outer plexiform layer; INL: inner nuclear layer; ONL: outer nuclear layer; PIS: photoreceptor inner segments; POS: photoreceptor outer segments; G: granuloma. (Retinas: n =3, control; n =3, IPMe-immunized group at each time point; n =4, IRBP-immunized group at each time point).


Figure 2




Figure 2 : 

Nitrite production in vivo (in plasma) during interphotoreceptor retinoid binding protein (IRBP) and interphotoreceptor matrix extract (IPMe)-induced experimental autoimmune uveitis. During IRBP-induced experimental model of autoimmune uveitis (EAU) (magenta histogram) and IPMe-induced EAU (yellow histogram), the in vivo nitrite production pattern shows significantly elevated amounts on the three stages of EAU (Day 7, 14 and 21 post immunization) when compared to control rats (non-immunized). Note that maximal nitrite production in vivo is observed on day 14 after immunization for IRBP-induced EAU and on day 7 post immunization for IPMe-immunized EAU. All results are expressed as mean±standard deviation. (Control, n =3; IRBP-immunized group at each time point, n =4; IPMe-immunized group at each time point, n =3). P values from LSD post-hoc Anova test are indicated (NS: not significant, **P 0.001, ***P 0.0001).


Figure 3




Figure 3 : 

Comparing nitrite production kinetics in vivo with histological disorders evolution during interphotoreceptor matrix extract (IPMe) and interphotoreceptor retinoid binding protein (IRBP)-induced experimental model of autoimmune uveitis (EAU). (A) During IRBP-induced EAU and (B) IPMe-induced EAU, maximal nitrite production in vivo (respectively on days 14 and 7 post immunization) is detected before the appearance of severe histological disorders (respectively on days 21 and 14 post immunization). For histological grades: grade 0 refers to normal retina morphology; grade 1 refers to a severe retina structure disruption.


Figure 4




Figure 4 : 

Nitrite production in situ (in homogenates of eyes) during IRBP-induced experimental autoimmune uveitis. Nitrite production pattern in situ, shows significantly high levels on day 14 and 21 post immunization, when compared to control animals (day 0). All results are expressed as mean±standard deviation. (Control, n =3; IRBP-immunized group at each time point, n =3). P values from Student’s unpaired t test are indicated (NS: not significant, **P 0.001).


Figure 5




Figure 5 : 

Comparing nitrite production kinetics in situ with histological disorders evolution during interphotoreceptor retinoid binding protein (IRBP)-induced experimental model of autoimmune uveitis (EAU). During IRBP-induced EAU, significant elevated amounts of nitrites are detected at the initial phase (day 14 post immunization) and at the peak of the disease (day 21 post immunization). For histological grades: grade 0 refers to normal retina morphology; grade 1 refers to a severe retina structure disruption.

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