INTRODUCTION: Autoimmune uveitis is a group of HLA-associated inflammatory diseases of the eye, prevalent worldwide, that may cause blindness. It can be limited to the eye, or associated with a systemic syndrome. Furthermore, patients suffering from uveitis exhibit high serum and local nitric oxide (NO) levels as a consequence of cellular responses to immunologically privileged antigens within the eye such as interphotoreceptor retinoid binding protein (IRBP). To investigate NO production kinetics in autoimmune uveitis and its implication in mechanisms of ocular pathogenesis, we first attempted to develop an experimental model of autoimmune uveitis (EAU) on the Wistar rat, using the whole bovine retinal interphotoreceptor matrix extract (IPMe) and isolated IRBP. MATERIAL AND METHODS: Female Wistar rats (n=24) were divided into three experimental groups: "control rats" (n=3) consisting of non-immunized animals, "IRBP-immunized rats" (n=12) and "IPMe-immunized rats" (n=9), which received a subcutaneous injection, respectively, of 13 μg IRBP and 100 μg IPMe emulsified in complete Freund's adjuvant. On days 7, 14 and 21 post immunization, the rats were sacrificed. Nitrites were assessed in plasma and in homogenate of eyes using the Griess reaction. Meanwhile, eyes were collected for histological studies. RESULTS: Our results show the sensitivity of the Wistar strain to both IPMe and IRBP-induced EAU. In fact, we observed histological disorders affecting the retinal tissue in both models of EAU. On the other hand, a significantly increased production of NO in plasma and homogenate of eyes was also observed in comparison to the control group. Moreover, we noted with interest that maximal production of NO occurs prior to the alteration of retinal tissue. CONCLUSION: In summary, our results suggest the early involvement of NO in the mechanisms of pathogenesis of EAU. NO can be considered as a key bio-marker of poor prognosis in ocular autoimmune inflammation.
INTRODUCTION:Autoimmune uveitis is a group of HLA-associated inflammatory diseases of the eye, prevalent worldwide, that may cause blindness. It can be limited to the eye, or associated with a systemic syndrome. Furthermore, patients suffering from uveitis exhibit high serum and local nitric oxide (NO) levels as a consequence of cellular responses to immunologically privileged antigens within the eye such as interphotoreceptor retinoid binding protein (IRBP). To investigate NO production kinetics in autoimmune uveitis and its implication in mechanisms of ocular pathogenesis, we first attempted to develop an experimental model of autoimmune uveitis (EAU) on the Wistar rat, using the whole bovine retinal interphotoreceptor matrix extract (IPMe) and isolated IRBP. MATERIAL AND METHODS: Female Wistar rats (n=24) were divided into three experimental groups: "control rats" (n=3) consisting of non-immunized animals, "IRBP-immunized rats" (n=12) and "IPMe-immunized rats" (n=9), which received a subcutaneous injection, respectively, of 13 μg IRBP and 100 μg IPMe emulsified in complete Freund's adjuvant. On days 7, 14 and 21 post immunization, the rats were sacrificed. Nitrites were assessed in plasma and in homogenate of eyes using the Griess reaction. Meanwhile, eyes were collected for histological studies. RESULTS: Our results show the sensitivity of the Wistar strain to both IPMe and IRBP-induced EAU. In fact, we observed histological disorders affecting the retinal tissue in both models of EAU. On the other hand, a significantly increased production of NO in plasma and homogenate of eyes was also observed in comparison to the control group. Moreover, we noted with interest that maximal production of NO occurs prior to the alteration of retinal tissue. CONCLUSION: In summary, our results suggest the early involvement of NO in the mechanisms of pathogenesis of EAU. NO can be considered as a key bio-marker of poor prognosis in ocular autoimmune inflammation.
Authors: Brenda Fernanda Moreira Castro; Carolina Nunes da Silva; Lídia Pereira Barbosa Cordeiro; Sarah Pereira de Freitas Cenachi; Daniel Vitor Vasconcelos-Santos; Renes Resende Machado; Luiz Guilherme Dias Heneine; Luciana Maria Silva; Armando Silva-Cunha; Silvia Ligório Fialho Journal: Curr Res Pharmacol Drug Discov Date: 2022-05-11