Purchase this article with an account.
Rashid M. Mahdi, Cheng-Rong Yu, Ahjoku Amadi-Obi, Charles E. Egwuagu; Socs1 Has Neuroprotective Functions And Mitigate Retina Damage During Uveitis By Rendering Retinal Cells Less Responsive To Cytokine Signaling. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2948.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Inflammation in the brain or neuroretina presents unique challenges because the ultimate goal of eliminating the pathogen must be counterbalanced by the need to limit exuberant inflammatory responses that might compromise functional integrity exquisitely delicate tissues in these organ systems. Suppressors of cytokine signaling (SOCS) proteins play essential roles in regulating the intensity and duration of cytokine signals in many tissues. In this study we have investigated whether SOCS1 plays a role in mitigating retina damage caused by the copious amounts of proinflammatory cytokines secreted in the neuroretina during uveitis.
To investigate potential role of SOCS1 in ocular inflammatory diseases we generated transgenic rats over-expressing SOCS1 in the retina (SOCS1-Tg) and mice with conditional deletion of SOCS1 (SOCS1KO) in retinal cells. We induced experimental autoimmune uveitis (EAU) in WT and mutant rat and mouse strains by active immunization with IRBP or adoptive transfer. Severity and progression of EAU were assessed by fundoscopy and histopathology. Proliferation and cytokine expression of lymphocytes and retinal cells were analyzed by qPCR, RT-PCR, intracellular cytokine staining and western blot assays.
We show that EAU in SOCS1-Tg rats was less severe as fundoscopic and histological analysis revealed less pathological changes in the retina. We further show that the mice with SOCS1 deficiency express higher levels of Mig, IP-10, LARK, CCR6, and CXCR3. On the other hand, the relative resistance of SOCS1-Tg rats to EAU correlated with substantial reduction of CCl17, CCL20, CXCL9, and CXCL10 expression, decrease in numbers of inflammatory cells in the retina and diminished ability of retinal cells to respond to cytokine signaling. In addition, SOCS1-Tg rats did not develop retinal lesions following transfer of IRBP-specific autoreactive T cells that induced EAU and retinal damage in WT rat retina.
Our data indicate that SOCS1 may mitigate retina damage during intraocular inflammation by rendering retinal cells less responsive to cytokine signaling. Our results further suggest that SOCS1 may have neuroprotective functions and that targeted delivery of SOCS1 into retinal cells may be of therapeutic value in the treatment of chronic intraocular inflammatory diseases.
This PDF is available to Subscribers Only