Abstract
Elevated levels of inflammatory cytokines in the vitreous of patients with chronic intraocular inflammatory (uveitis) have long been suspected to contribute to the pathogenesis of retinal degenerative diseases. However, direct connection between chronic inflammation and development of retinal degenerative diseases has been difficult to establish because we lack an appropriate animal model of co-existing chronic intraocular inflammation and neurodegeneration. This report discusses new developments in immunological and diabetic research that suggest that persistent secretion of pro-inflammatory cytokines during uveitis might induce insulin resistance and retinal degenerative changes that contribute to the pathogenesis of Diabetic Retinopathy (DR), a retinal dystrophy of significant public health importance.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS et al (2006) Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 55(9):2401–2411
Meleth AD, Agron E, Chan CC, Reed GF, Arora K, Byrnes G et al (2005) Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 46(11):4295–4301
Oh HM, Yu CR, Lee Y, Chan CC, Maminishkis A, Egwuagu CE (2011) Autoreactive memory CD4+ T lymphocytes that mediate chronic uveitis reside in the bone marrow through STAT3-dependent mechanisms. J Immunol 187(6):3338–3346
Egwuagu CE, Mahdi RM, Chan CC, Sztein J, Li W, Smith JA et al (1999) Expression of interferon-gamma in the lens exacerbates anterior uveitis and induces retinal degenerative changes in transgenic Lewis rats. Clin Immunol 91(2):196–205
Nussenblatt RB (1991) Proctor lecture. Experimental autoimmune uveitis: mechanisms of disease and clinical therapeutic indications. Invest Ophthalmol Vis Sci 32(13):3131–3141
Taniguchi CM, Emanuelli B, Kahn CR (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7(2):85–96
Naka T, Fujimoto M, Kishimoto T (1999) Negative regulation of cytokine signaling: STAT-induced STAT inhibitor. Trends Biochem Sci 24(10):394–398
Hilton DJ (1999) Negative regulators of cytokine signal transduction. Cell Mol Life Sci 55(12):1568–1577
Emanuelli B, Glondu M, Filloux C, Peraldi P, Van Obberghen E (2004) The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells. Diabetes 53(Suppl 3):S97–S103
Liu X, Mameza MG, Lee YS, Eseonu CI, Yu CR, Kang Derwent JJ et al (2008) Suppressors of cytokine-signaling proteins induce insulin resistance in the retina and promote survival of retinal cells. Diabetes 57(6):1651–1658
Liu X, Lee YS, Yu CR, Egwuagu CE (2008) Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J Immunol 180(9):6070–6076
Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB et al (2007) T(H)17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13(6):711–718
Egwuagu CE, Mahdi RM, Chan CC, Sztein J, Li W, Smith JA et al (1999) Expression of interferon-gamma in the lens exacerbates anterior uveitis and induces retinal degenerative changes in transgenic Lewis rats. Clin Immunol 91(2):196–205
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this paper
Cite this paper
Egwuagu, C. (2014). Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_53
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3209-8_53
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3208-1
Online ISBN: 978-1-4614-3209-8
eBook Packages: MedicineMedicine (R0)