Endoplasmic reticulum stress and inflammation: Mechanisms and implications in diabetic retinopathy

Journal of Ocular Biology, Diseases, and Informatics

Volumn 4, Issue 1-2, 2011, Pages 51-61

  Zhang, Sarah X ^a,b   Sanders, Emily ^a,b   Wang, Joshua J ^a,b  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

Author keywords

Diabetic retinopathy; ER stress; Inflammation; Unfolded protein response

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ACTIVATING TRANSCRIPTION FACTOR 6; CCAAT ENHANCER BINDING PROTEIN; GLUCOSE REGULATED PROTEIN 78; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; PKR LIKE ENDOPLASMIC RETICULUM KINASE; PROTEIN IRE1; PROTEIN SERINE THREONINE KINASE; STRESS ACTIVATED PROTEIN KINASE; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN; X BOX BINDING PROTEIN 1;

APOPTOSIS; BLOOD RETINA BARRIER; CYTOKINE RELEASE; DIABETIC MACULAR EDEMA; DIABETIC RETINOPATHY; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; ENDOPLASMIC RETICULUM STRESS; HYPERGLYCEMIA; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PERICYTE; PRIORITY JOURNAL; PROTEIN FOLDING; RETINA ISCHEMIA; RETINA NEOVASCULARIZATION; RETINITIS; REVIEW; STREPTOZOCIN DIABETES; TIGHT JUNCTION; UNFOLDED PROTEIN RESPONSE;

EID: 84863987259     PISSN: 19368437     EISSN: 19368445     Source Type: Journal    
DOI: 10.1007/s12177-011-9075-5     Document Type: Review

References (111)

1. American Diabetes Association. Implications of the diabetes control and complications trial. Diabetes Care. 2003;26 Suppl 1:25-7.
2. Danaei G, FinucaneMM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378(9785):31-40.
3. Fong DS, Aiello L, Gardner TW, et al. Diabetic retinopathy. Diabetes Care. 2003;26(1):226-9. (Pubitemid 36934461)
4. American Diabetes Association. Diabetic nephropathy. Diabetes Care. 2000;23 Suppl 1:S69-72.
5. The Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477-85.
6. The Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004;122(4):552-63.
7. Ferris 3rd FL. Results of 20 years of research on the treatment of diabetic retinopathy. Prev Med. 1994;23(5):740-2.
8. National Eye Institute (2004) Statement on the prevalence of diabetic retinopathy and age-related macular degeneration among Hispanic/Latino Americans. http://www.nei.nih.gov/news/statements/latinostudy.asp.
9. Rein DB, Zhang P, Wirth KE, et al. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006;124(12):1754-60. (Pubitemid 44920172)
10. Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Sci. 2004;306:457-61. (Pubitemid 39372439)
11. Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Sci. 2006;313(5790):1137-40. (Pubitemid 44300242)
12. Song B, Scheuner D, Ron D, Pennathur S, Kaufman RJ. Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. J Clin Invest. 2008;118(10):3378-89.
13. Li J, Wang JJ, Yu Q, Wang M, Zhang SX. Endoplasmic reticulum stress is implicated in retinal inflammation and diabetic retinopathy. FEBS Lett. 2009;583:1521-7.
14. Li J, Wang JJ, Zhang SX. Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein 1. J Biol Chem. 2011;286(6):4912-21.
15. Gardner TW, Antonetti DA. Novel potential mechanisms for diabetic macular edema: leveraging new investigational approaches. Curr Diab Rep. 2008;8(4):263-9.
16. Xu H-Z, Le Y-Z. Significance of outer blood-retina barrier breakdown in diabetes and ischemia. Invest Ophthalmol Vis Sci. 2011;52 (5):2160-4.
17. Martin PM, Roon P, Van Ells TK, Ganapathy V, Smith SB. Death of retinal neurons in streptozotocin-induced diabetic mice. Invest Ophthalmol Vis Sci. 2004;45(9):3330-6. (Pubitemid 39121873)
18. Joussen AM, Poulaki V, Tsujikawa A, et al. Suppression of diabetic retinopathy with angiopoietin-1 [comment]. Am J Pathol. 2002;160(5):1683-93. (Pubitemid 34525648)
19. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes. 1998;47(12):1953-9. (Pubitemid 28549205)
20. Antonetti DA, Barber AJ, Bronson SK, et al. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes. 2006;55(9):2401-11. (Pubitemid 44871140)
21. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 1998;102:783-91. (Pubitemid 28399611)
22. Kusner LL, Sarthy VP, Mohr S. Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase: a role in high glucose-induced apoptosis in retinal Muller cells. Invest Ophthalmol Vis Sci. 2004;45:1553-61. (Pubitemid 38859337)
23. Sugimoto M, Sasoh M, Ido M, Wakitani Y, Takahashi C, Uji Y. Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy. Ophthalmol. 2005;219(6):379-85. (Pubitemid 41628301)
24. Yonemura D, Tsuzuki K. Electroretinogram in diabetic retinopathy. Arch Ophthalmol. 1962;68(1):19-24.
25. Sokol S, Moskowitz A, Skarf B, Evans R, Molitch M, Senior B. Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol. 1985;103(1):51-4. (Pubitemid 15152624)
26. Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal antiinflammatory drugs prevent early diabetic retinopathy via TNFalpha suppression. FASEB J. 2002;16(3):438-40.
27. Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol. 2002;133(1):70-7. (Pubitemid 34076505)
28. Zhang SX, Wang JJ, Gao G, Shao C, Mott R, J-x M. Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. FASEB J. 2006;20(2):323-5. (Pubitemid 46671158)
29. Qaum T, Xu Q, Joussen AM, et al. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci. 2001;42(10):2408-13. (Pubitemid 32848873)
30. Joussen AM, Poulaki V, Qin W, et al. Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol. 2002;160(2):501-9. (Pubitemid 34160327)
31. Koizumi K, Poulaki V, Doehmen S, et al. Contribution of TNFalpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo. Invest Ophthalmol Vis Sci. 2003;44(5):2184-91. (Pubitemid 36520316)
32. Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT. Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol. 2008;172(5):1411-8. (Pubitemid 351671553)
33. De La Cruz JP, Gonzalez-Correa JA, Guerrero A, De La Cuesta FS. Pharmacological approach to diabetic retinopathy. Diabetes Metabol Res Rev. 2004;20(2):91-113.
34. Kowluru RA, Chan PS. Oxidative stress and diabetic retinopathy. Exp Diabetes Res. 2007;2007:43603.
35. Chen P, Guo AM, Edwards PA, Trick G, Scicli AG. Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis. Am J Physiol Regul Integr Comp Physiol. 2007;293(4): R1619-29. (Pubitemid 47535780)
36. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8 (7):519-29. (Pubitemid 46985379)
37. Todd DJ, Lee AH, Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol. 2008;8 (9):663-74.
38. Gorlach A, Klappa P, Kietzmann T. The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid Redox Signal. 2006;8(9-10):1391-418. (Pubitemid 44726319)
39. Bouman L, Schlierf A, Lutz A, et al. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death Diff. 2010;18:769-82.
40. Sundar Rajan S, Srinivasan V, Balasubramanyam M, Tatu U. Endoplasmic reticulum (ER) stress & diabetes. Indian J Med Res. 2007;125(3):411-24. (Pubitemid 46805455)
41. Lindholm D, Wootz H, Korhonen L. ER stress and neurodegenerative diseases. Cell Death Differ. 2006;13(3):385-92.
42. Szegezdi E, Duffy A, O'Mahoney ME, et al. ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun. 2006;349(4):1406-11. (Pubitemid 44416413)
43. Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999;397(6716):271-4. (Pubitemid 29051178)
44. Tirasophon W, Welihinda AA, Kaufman RJ. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 1998;12(12):1812-24. (Pubitemid 28304334)
45. Calfon M, Zeng H, Urano F, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002;415(6867):92-6. (Pubitemid 34062456)
46. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2002;2(6):326-32.
47. Ng D, Watowich S, Lamb R. Analysis in vivo of GRP78-BiP/ substrate interactions and their role in induction of the GRP78-BiP gene. Mol Biol Cell. 1992;3(2):143.
48. Haze K, Okada T, Yoshida H, et al. Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response. Biochem J. 2001;355(Pt 1):19.
49. Schroder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem. 2005;74:739-89. (Pubitemid 40995523)
50. Paschen W, Frandsen A. Endoplasmic reticulum dysfunction-a common denominator for cell injury in acute and degenerative diseases of the brain? J Neurochem. 2001;79(4):719-25. (Pubitemid 33086509)
51. Rao RV, EllerbyHM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 2004;11(4):372-80. (Pubitemid 38489415)
52. Jing G, Wang, J, Zhang, SX. ER stress and apoptosis: a new mechanism for retinal cell death. Exp Diabetes Res 2012. doi:10.1155/2012/589589.
53. Mosbah B, Alfany-Fernandez I, Martel C, et al. Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy undder ischemia-reperfusion. Cell Death and Dis. 2010;1:e52.
54. Gotoh T, Endo M, Oike Y. Endoplasmic reticulum stress-related inflammation and cardiovascular disease. Int J Inflamm. 2011;2011:259462.
55. Urano F, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Sci. 2000;287(5453):664-6. (Pubitemid 30070916)
56. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol cell. 2000;5(5):897-904.
57. Harding HP, Zhang Y, Zeng H, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003;11(3):619-33. (Pubitemid 36385118)
58. Harding HP, Novoa I, Zhang Y, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000;6(5):1099-108.
59. Vattem KM, Wek RC. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc Natl Acad Sci USA. 2004;101(31):11269-74. (Pubitemid 39038336)
60. Marciniak SJYC, Oyadomari S, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004;18(24):3066-77. (Pubitemid 39658175)
61. Giorgi C, Stefani D, Bononi A, Rizzuto R, Pinton P. Structural and functional link between the mitochondrial network and the endoplasmic reticulum. Int J Biochem Cell Biol. 2009;41 (10):1817-27.
62. Namba T, Tanaka K-I, Ito Y, et al. Positive role of CCAAT/ enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis. Am J Pathol. 2009;174(5):1786-98.
63. Endo M, Mori M, Akira S, Gotoh T. C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation. J Immunol. 2006;176(10):6245-53.
64. Rahman SM, Schroeder-Gloeckler JM, et al. CCAAT/enhancing binding protein β deletion in mice attenuates inflammation, endoplasmic reticulum stress, and lipid accumulation in dietinduced nonalcoholic steatohepatitis. Hepatology. 2007;45(5):1108-17. (Pubitemid 46775772)
65. Yamamoto K, Takahara K, Oyadomari S, et al. Induction of liver steatosis and lipid droplet formation in ATF6α-knockout mice burdened with pharmacological endoplasmic reticulum stress. Mol Biol Cell. 2010;21(17):2975-86.
66. Chen X, Shen J, Prywes R. The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J Biochem. 2002;277:13045-52. (Pubitemid 34952673)
67. Yamamoto KST, Matsui T, Sato M, et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell. 2007;13:365-76. (Pubitemid 47308680)
68. Wu J, Rutkowski DT, Dubois M, et al. ATF6α optimizes longterm endoplasmic reticulum function to protect cells from chronic stress. Dev Cell. 2007;13(3):351-64. (Pubitemid 47308675)
69. Martindale J, Fernandez R, Thuerauf D, et al. Endoplasmic reticulum stress gene induction and protection from ischemia/reperfusion injury in the hearts of transgenic mice with a tamoxifenregulated form of ATF6. Circ Res. 2006;98(9):1186-93. (Pubitemid 43948105)
70. Thameem F, Farook VS, Bogardus C, Prochazka M. Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians. Diabetes. 2006;55(3):839-42. (Pubitemid 43343245)
71. Tang L, Zhang Y, Jiang Y, et al. Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes. Exp Biol Med. 2011;236(9):1051-63.
72. Yan S, Zheng C, Chen Z-q, et al. Expression of endoplasmic reticulum stress-related factors in the retinas of diabetic rats. Exp Dia Res, 2012; (in press)
73. Adachi T, Yasuda H, Nakamura S, et al. Endoplasmic reticulum stress induces retinal endothelial permeability of extracellularsuperoxide dismutase. Free Radical Res. 2011;45(9):1083-92.
74. Smith LE, Wesolowski E, McLellan A, et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35 (1):101-11. (Pubitemid 24046832)
75. Zhang SX, Ma J-X, Sima J, et al. Genetic difference in susceptibility to the blood-retina barrier breakdown in diabetes and oxygen-induced retinopathy. Am J Pathol. 2005;166(1):313-21. (Pubitemid 40051683)
76. Zhang SX, Wang JJ, Dashti A, et al. Pigment epithelium-derived factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J Mol Endocrinol. 2008;41(3):135-43.
77. Zhong Y, Wang JJ, Zhang SX. Intermittent but not constant high glucose induces ER stress and inflammation in human retinal pericytes Adv Exp Med Biol 2012;723:285-92.
78. Ikesugi K, Mulhern ML, Madson CJ, et al. Induction of endoplasmic reticulum stress in retinal pericytes by glucose deprivation. Curr Eye Res. 2006;31(11):947-53.
79. Ghosh R, Ghosh R, Lipson KL, et al. Transcriptional regulation of VEGF-A by the unfolded protein reponse pathway. PLoS One. 2010;5(3).
80. Zhou Q, Zouh M, Lou A, Xie D, Hou F. Advanced oxidation protein products induce inflammatory response and insulin resistance in cultured adipocytes via induction of endoplasmic reticulum stress. Cell Physiol Biochem. 2010;26:775-86.
81. Fougeray S, et al. Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response. Cell Death Dis 2012; (in press).
82. Mahadevan N, et al. Transmission of endoplasmic reticulum stress and pro-inflammation from tumor cells to myeloid cells. Proc Natl Acad Sci USA. 2011;108(16):6561-6.
83. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455-62.
84. Kaser A, Blumberg RS. Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease. Seminars Immunol. 2009;21(3):156-63.
85. Hotamisligil GH. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140(6):900-17.
86. Senger DRLS, Claffey KP, et al. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol. 1996;149:293-305. (Pubitemid 26231000)
87. Tang J, Kern TS. Inflammation and diabetic retinopathy. Progress in Retinal and Eye Research. 2011;30:343-58.
88. Drogat B, Auguste P, Nguyen DT, et al. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Res. 2007;67(14):6700-7. (Pubitemid 47105516)
89. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci USA. 2009;106(39):16657-62.
90. Roybal CN, Yang S, Sun CW, et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004;279(15):14844-52. (Pubitemid 38618874)
91. Roybal CN, Hunsaker LA, Barbash O, Vander Jagt DL, Abcouwer SF. The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism. J Biol Chem. 2005;280(21):20331-9. (Pubitemid 40776731)
92. Malabanan KP, Kanellakis P, Bobik A, Khachigian LM. Activation transcription factor-4 induced by fibroblast growth factor-2 regulates vascular endothelial growth factor-A transcription in vascular smooth muscle cells and mediates intimal thickening in rat arteries following balloon injury. Circ Res. 2008;103(4):378-87.
93. Karin M, Gallagher E. From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance. IUBMB Life. 2005;57(4-5):283-95. (Pubitemid 40904256)
94. Guma M, Rius J, Duong-Polk KX, Haddad GG, Lindsey JD, Karin M. Genetic and pharmacological inhibition of JNK ameliorates hypoxia-induced retinopathy through interference with VEGF expression. Proc Natl Acad Sci USA. 2009;106(21):8760-5.
95. Kim H-T, QiangW, Liu N, Scofield VL,Wong PK, Stoica G. Upregulation of astrocyte cyclooxygenase-2, CCAAT/enhancerbinding protein, glucose-related protein 78, eukaryotic initiation factor 2α, and c-Jun N-terminal kinase by a neurovirulent murine retrovirus. J Neurovirol. 2005;11(2):166-79. (Pubitemid 40852424)
96. Urano FWX, Bertolotti A, Zhang Y, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 2000;287:664-6. (Pubitemid 30070916)
97. Verma G, Datta M. IL-1- induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells. Apoptosis. 2010;2010:1-13.
98. Chen YM, Chiang WC, Lin SL,Wu KD, Tsai TJ, Hsieh BS. Dual regulation of tumor necrosis factor-alpha-induced CCL2/monocyte chemoattractant protein-1 expression in vascular smooth muscle cells by nuclear factor-kappaB and activator protein-1: modulation by type III phosphodiesterase inhibition. J Pharmacol Exp Ther. 2004;309(3):978-86.
99. Chen W, Esselman WJ, Jump DB, Busik JV. Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci. 2005;46(11):4342-7. (Pubitemid 44264641)
100. Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res. 2007;2007:95103.
101. Zheng L, Howell SJ, Hatala DA, Huang K, Kern TS. Salicylatebased anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes. 2007;56(2):337-45.
102. Mitamura Y, Harada T, Harada C, et al. NF-kappaB in epiretinal membranes after human diabetic retinopathy. Diabetologia. 2003;46(5):699-703. (Pubitemid 36808190)
103. Kaji Y, Usui T, Ishida S, et al. Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products. Invest Ophthalmol Vis Sci. 2007;48(2):858-65. (Pubitemid 351260723)
104. Yamazaki HHN, Hayakawa K, Tagawa Y, et al. Activation of the Akt-NF-kappaB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol. 2009;183:1480-7.
105. Jiao P,Ma J, Feng B, et al. FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKβ pathways. Obesity. 2011;19:483-90.
106. Ko MK, Saraswathy S, Parikh JG, Rao NA. The role of TLR4 activation in photoreceptor mitochondrial oxidative stress. Invest Ophthalmol Vis Sci. 2011;52:5824-35.
107. Jiang G, Ke Y, Sun D, Wang Y, Kaplan HJ, Shao H. Regulatory role of TLR ligands on the activation of autoreactive t cells by retinal astrocytes. Invest Ophthalmol Vis Sci. 2009;50:4769-76.
108. Kumar MV, Nagineni CN, Chin MS, Hooks JJ, Detrick B. Innate immunity in the retina: toll-like receptor (TLR) signaling in human retinal pigment epithelial cells. J Neuroimmunol. 2004;153:7-15. (Pubitemid 38950922)
109. Dvoriantchikova G, Barakat DJ, Hernandez E, Shestopalov V. Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. Mol Vis. 2010;16:1907-12.
110. Woo CW, Cui D, Arellano J, et al. Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling. Nat Cell Biol. 2009;11:1473-80.
111. Martinon FC, Lee X, Glimcher LH. TLR activation of the transcription factor XBP1 regulates innate immune response in macrophages. Nat Immunol. 2010;11:411-8.