[1]张敬法.炎症在糖尿病视网膜病变中的作用:发病机制及治疗策略[J].眼科新进展,2024,44(1):001-12.[doi:10.13389/j.cnki.rao.2024.0001]
 ZHANG Jingfa.Role of inflammation in diabetic retinopathy: pathogenesis and treatment strategies[J].Recent Advances in Ophthalmology,2024,44(1):001-12.[doi:10.13389/j.cnki.rao.2024.0001]
点击复制

炎症在糖尿病视网膜病变中的作用:发病机制及治疗策略/HTML
分享到:

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
44卷
期数:
2024年1期
页码:
001-12
栏目:
述评
出版日期:
2024-01-05

文章信息/Info

Title:
Role of inflammation in diabetic retinopathy: pathogenesis and treatment strategies
作者:
张敬法
200080 上海市,上海交通大学医学院附属第一人民医院眼科
Author(s):
ZHANG Jingfa
Department of Ophthalmology,Shanghai General Hospital (Shanghai First People’s Hospital),Shanghai Jiao Tong University,School of Medicine,Shanghai 200080,China
关键词:
糖尿病视网膜病变炎症炎症因子炎症细胞小胶质细胞
Keywords:
diabetic retinopathy inflammation inflammatory factors inflammatory cells microglia
分类号:
R774.1
DOI:
10.13389/j.cnki.rao.2024.0001
文献标志码:
A
摘要:
糖尿病视网膜病变(DR)被认为是一种慢性中低度炎症性(微炎症)疾病。炎症贯穿DR发病全过程,表现为全身及眼局部炎症生物标志物增加。在DR患者眼中,促炎介质增加,如白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)等增加;炎症细胞活化并增多,如视网膜中活化的小胶质细胞、Müller细胞和单核巨噬细胞浸润等。此外,免疫细胞也参与了DR的发病,如循环T淋巴细胞参与白细胞瘀滞。这些研究结果表明DR具有慢性炎症的病因,多种炎症相关因素共同参与、互相影响,导致血-视网膜屏障破坏和神经元损伤,加重DR的进展。因此,个体化抗炎治疗在DR治疗中具有重要意义。
Abstract:
Diabetic retinopathy (DR) is considered to be a chronic medium- and low-grade inflammatory disease (microinflammation). Inflammation runs through the entire process of DR, manifesting as an increase in ocular and systemic inflammation biomarkers. In the eyes of DR patients, there is an increase in pro-inflammatory mediators, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α, as well as activated and increased number of inflammatory cells, such as activated microglia, Müller cells in the retina, and infiltration of mononuclear macrophage. In addition, immunocytes are also involved in the pathogenesis of DR, such as the involvement of circulating T cells in leukostasis. These indicate that chronic inflammation is an inducing factor of DR, with multiple inflammation-related factors participating and influencing each other, leading to the destruction of the blood-retinal barrier and neuronal injury and exacerbating the development of DR. Therefore, personalized anti-inflammatory therapy is of great significance in the treatment of DR.

参考文献/References:

[1] TANG J,KERN T S.Inflammation in diabetic retinopathy[J].Prog Retin Eye Res,2011,30(5):343-358.
[2] SONG J,CHEN S,LIU X,DUAN H,KONG J,LI Z.Relationship between C-reactive protein level and diabetic retinopathy:a systematic review and meta-analysis[J].PLoS One,2015,10(12):e0144406.
[3] WOO S J,AHN S J,AHN J,PARK K H,LEE K.Elevated systemic neutrophil count in diabetic retinopathy and diabetes:a hospital-based cross-sectional study of 30 793 Korean subjects[J].Invest Ophthalmol Vis Sci,2011,52(10):7697.
[4] GUSTAVSSON C,AGARDH C D,AGARDH E.Profile of intraocular tumour necrosis factor-α and interleukin-6 in diabetic subjects with different degrees of diabetic retinopathy[J].Acta Ophthalmol,2013,91(5):445-452.
[5] MIYAMOTO K,HIROSHIBA N,TSUJIKAWA A,OGURA Y.In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats[J].Invest Ophthalmol Vis Sci,1998,39(11):2190-2194.
[6] JOUSSEN A M,POULAKI V,LE M L,KOIZUMI K,ESSER C,JANICKI H,et al.A central role for inflammation in the pa-thogenesis of diabetic retinopathy[J].FASEB J,2004,18(12):1450-1452.
[7] ALTMANN C,SCHMIDT M.The role of microglia in diabetic retinopathy:inflammation,microvasculature defects and neurodegeneration[J].Int J Mol Sci,2018,19(1):110.
[8] KA?TELAN S, ORE?KOVI? I, BI??AN F, KA?TELAN H, GVEROVI? ANTUNICA A.Inflammatory and angiogenic biomarkers in diabetic retinopathy[J].Biochem Med (Online),2020,30(3):385-399.
[9] ASCASO F J,HUERVA V,GRZYBOWSKI A.The role of inflammation in the pathogenesis of macular edema secondary to retinal vascular diseases[J].Mediat Inflamm,2014,2014:1-6.
[10] TONADE D,LIU H,PALCZEWSKI K,KERN T S.Photoreceptor cells produce inflammatory products that contribute to retinal vascular permeability in a mouse model of diabetes[J].Diabetologia,2017,60(10):2111-2120.
[11] QIU A W,HUANG D R,LI B,FANG Y,ZHANG W W,LIU Q H.IL-17A injury to retinal ganglion cells is mediated by retinal Müller cells in diabetic retinopathy[J].Cell Death Dis,2021,12(11):1057.
[12] XU H,CHEN M.Diabetic retinopathy and dysregulated innate immunity[J].Vis Res,2017,139:39-46.
[13] IKEDA T,NAKAMURA K,KIDA T,OKU H.Possible roles of anti-type II collagen antibody and innate immunity in the development and progression of diabetic retinopathy[J].Graefes Arch Clin Exp Ophthalmol,2022,260(2):387-403.
[14] TANG D,KANG R,COYNE C B,ZEH H J,LOTZE M T.PAMPs and DAMPs:signal 0s that spur autophagy and immunity[J].Immunol Rev,2012,249(1):158-175.
[15] KARMAKAR M,KATSNELSON M A,DUBYAK G R,PEARLMAN E.Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP[J].Nat Commun,2016,7:10555.
[16] FU Q,WU J,ZHOU X Y,JI M H,MAO Q H,LI Q,et al.NLRP3/caspase-1 pathway-induced pyroptosis mediated cognitive deficits in a mouse model of sepsis-associated encephalopathy[J].Inflammation,2019,42(1):306-318.
[17] ZHANG Y,LV X,HU Z,YE X,ZHENG X,DING Y,et al.Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction[J].Cell Death Dis,2017,8(7):e2941.
[18] TROTTA M C,MAISTO R,GUIDA F,BOCCELLA S,LUONGO L,BALTA C,et al.The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome[J].PLoS One,2019,14(1):e0211005.
[19] LI Y,SMITH D,LI Q,SHEIBANI N,HUANG S,KERN T,et al.Antibody-mediated retinal pericyte injury:implications for diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2012,53(9):5520.
[20] NAKAIZUMI A,FUKUMOTO M,KIDA T,SUZUKI H,MORISHITA S,SATOU T,et al.Measurement of serum and vitreous concentrations of anti-type II collagen antibody in diabetic retinopathy[J].Clin Ophthalmol,2015,9:543-547.
[21] HUANG J,ZHOU Q.Identification of the relationship between hub genes and immune cell infiltration in vascular endothelial cells of proliferative diabetic retinopathy using bioinformatics methods[J].Dis Markers,2022,2022:1-21.
[22] LUTTY G A,CAO J,MCLEOD D S.Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid[J].Am J Pathol,1997,151(3):707-714.
[23] LAWRENCE M B,SMITH C W,ESKIN S G,MCINTIRE L V.Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium[J].Blood,1990,75(1):227-237.
[24] LONG E O.ICAM-1:getting a grip on leukocyte adhesion[J].J Immunol,2011,186(9):5021-5023.
[25] JOUSSEN A M,MURATA T,TSUJIKAWA A,KIRCHHOF B,BURSELL S E,ADAMIS A P.Leukocyte-mediated endothelial cell injury and death in the diabetic retina[J].Am J Pathol,2001,158(1):147-152.
[26] ROY S,KERN T S,SONG B,STUEBE C.Mechanistic insights into pathological changes in the diabetic retina[J].Am J Pathol,2017,187(1):9-19.
[27] FORRESTER J V,KUFFOVA L,DELIBEGOVIC M.The role of inflammation in diabetic retinopathy[J].Front Immunol,2020,11:583687.
[28] VAN DER WIJK A E,HUGHES J M,KLAASSEN I,VAN NOORDEN C J F,SCHLINGEMANN R O.Is leukostasis a crucial step or epiphenomenon in the pathogenesis of diabetic retinopathy?[J].J Leukoc Biol,2017,102(4):993-1001.
[29] MIYAMOTO K,KHOSROF S,BURSELL S E,ROHAN R,MURATA T,CLERMONT A C,et al.Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition[J].Proc Natl Acad Sci USA,1999,96(19):10836-10841.
[30] KOBAYASHI Y,YOSHIDA S,NAKAMA T,ZHOU Y,ISHIKAWA K,ARITA R,et al.Overexpression of CD163 in vitreous and fibrovascular membranes of patients with proliferative diabetic retinopathy:possible involvement of periostin[J].Br J Ophthalmol,2015,99(4):451-456.
[31] ABU EL-ASRAR A M,AHMAD A,ALLEGAERT E,SIDDIQUEI M M,GIKANDI P W,DE HERTOGH G,et al.Interleukin-11 overexpression and M2 macrophage density are associated with angiogenic activity in proliferative diabetic retinopathy[J].Ocul Immunol Inflamm,2020,28(4):575-588.
[32] GENG P,DING Y Y,QIU L,LU Y Y.Serum mannose-binding lectin is a strong biomarker of diabetic retinopathy in Chinese patients with diabetes[J].Diabetes Care,2015,38(5):868-875.
[33] ZHANG J,GERHARDINGER C,LORENZI M.Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy[J].Diabetes,2002,51(12):3499-3504.
[34] WANG H,FENG L,HU J,XIE C,WANG F.Differentiating vitreous proteomes in proliferative diabetic retinopathy using high-performance liquid chromatography coupled to tandem mass spectrometry[J].Exp Eye Res,2013,108:110-119.
[35] KARLSTETTER M,SCHOLZ R,RUTAR M,WONG W T,PROVIS J M,LANGMANN T.Retinal microglia:just bystander or target for therapy?[J].Prog Retin Eye Res,2015,45:30-57.
[36] XIE H,ZHANG C,LIU D,YANG Q,TANG L,WANG T,et al.Erythropoietin protects the inner blood-retinal barrier by inhibiting microglia phagocytosis via Src/Akt/cofilin signalling in experimental diabetic retinopathy[J].Diabetologia,2021,64(1):211-225.
[37] JIANG M,XIE H,ZHANG C,WANG T,TIAN H,LU L,et al.Enhancing fractalkine/CX3CR1 signalling pathway can reduce neuroinflammation by attenuating microglia activation in experimental diabetic retinopathy[J].J Cell Mol Med,2022,26(4):1229-1244.
[38] TAKEDA A,SHINOZAKI Y,KASHIWAGI K,OHNO N,ETO K,WAKE H,et al.Microglia mediate non-cell-autonomous cell death of retinal ganglion cells[J].Glia,2018,66(11):2366-2384.
[39] TANG L,ZHANG C,LU L,TIAN H,LIU K,LUO D,et al.Melatonin maintains inner blood-retinal barrier by regulating microglia via inhibition of PI3K/akt/Stat3/NF-κB signaling pathways in experimental diabetic retinopathy[J].Front Immunol,2022,13:831660.
[40] HOMBREBUENO J R,CHEN M,PENALVA R G,XU H.Loss of synaptic connectivity,particularly in second order neurons is a key feature of diabetic retinal neuropathy in the Ins2Akita mouse[J].PLoS One,2014,9(5):e97970.
[41] SIM R,STITT A W,GARDNER T W.Neurodegeneration in diabetic retinopathy:does it really matter?[J].Diabetologia,2018,61(9):1902-1912.
[42] GOTO Y,KAKIZAKI M,MASAKI N.Production of spontaneous diabetic rats by repetition of selective breeding[J].Tohoku J Exp Med,1976,119(1):85-90.
[43] OMRI S,BEHAR-COHEN F,DE KOZAK Y,SENNLAUB F,MAFRA VERISSIMO L,JONET L,et al.Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy[J].Am J Pathol,2011,179(2):942-953.
[44] LEE H,JANG H,CHOI Y A,KIM H C,CHUNG H.Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema[J].Invest Ophthalmol Vis Sci,2018,59(2):715.
[45] RBSAM A,PARIKH S,FORT P.Role of inflammation in diabetic retinopathy[J].Int J Mol Sci,2018,19(4):942.
[46] ZONG H,WARD M,MADDEN A,YONG P H,LIMB G A,CURTIS T M,et al.Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE)[J].Diabetologia,2010,53(12):2656-2666.
[47] GERHARDINGER C,COSTA M B,COULOMBE M C,TOTH I,HOEHN T,GROSU P.Expression of acute-phase response proteins in retinal Müller cells in diabetes[J].Invest Ophthalmol Vis Sci,2005,46(1):349.
[48] MU H,ZHANG X M,LIU J J,DONG L,FENG Z L.Effect of high glucose concentration on VEGF and PEDF expression in cultured retinal Müller cells[J].Mol Biol Rep,2009,36(8):2147-2151.
[49] HERNNDEZ C,SEGURA R M,FONOLLOSA A,CARRASCO E,FRANCISCO G,SIM R.Interleukin-8,monocyte chemoattractant protein-1 and IL-10 in the vitreous fluid of patients with proliferative diabetic retinopathy[J].Diabet Med,2005,22(6):719-722.
[50] PORTILLO J A C,LOPEZ CORCINO Y,MIAO Y,TANG J,SHEIBANI N,KERN T S,et al.CD40 in retinal Müller cells induces P2X7-dependent cytokine expression in macrophages/microglia in diabetic mice and development of early experimental diabetic retinopathy[J].Diabetes,2017,66(2):483-493.
[51] RIDET J L,PRIVAT A,MALHOTRA S K,GAGE F H.Reactive astrocytes:cellular and molecular cues to biological function[J].Trends Neurosci,1997,20(12):570-577.
[52] PEKNY M,WILHELMSSON U,PEKNA M.The dual role of astrocyte activation and reactive gliosis[J].Neurosci Lett,2014,565:30-38.
[53] ROTHHAMMER V,QUINTANA F J.Control of autoimmune CNS inflammation by astrocytes[J].Semin Immunopathol,2015,37(6):625-638.
[54] NOMA H,MIMURA T,YASUDA K,SHIMURA M.Role of inflammation in diabetic macular edema[J].Ophthalmologica,2014,232(3):127-135.
[55] TAGHAVI Y,HASSANSHAHI G,KOUNIS N G,KONIARI I,KHORRAMDELAZAD H.Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy:latest evidence and clinical considerations[J].J Cell Commun Signal,2019,13(4):451-462.
[56] AMADIO M,SCAPAGNINI G,LUPO G,DRAGO F,GOVONI S,PASCALE A.PKCβII/HuR/VEGF:a new molecular cascade in retinal pericytes for the regulation of VEGF gene expression[J].Pharmacol Res,2008,57(1):60-66.
[57] LIN M,CHEN Y,JIN J,HU Y,ZHOU K K,ZHU M,et al.Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Müller cells[J].Diabetologia,2011,54(6):1554-1566.
[58] BOULTON M,FOREMAN D,WILLIAMS G,MCLEOD D.VEGF localisation in diabetic retinopathy[J].Br J Ophthalmol,1998,82(5):561-568.
[59] PEACH C J,MIGNONE V W,ARRUDA M A,ALCOBIA D C,HILL S J,KILPATRICK L E,et al.Molecular pharmacology of VEGF-A isoforms:binding and signalling at VEGFR2[J].Int J Mol Sci,2018,19(4):1264.
[60] SHIBUYA M,CLAESSON-WELSH L.Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis[J].Exp Cell Res,2006,312(5):549-560.
[61] BAI Y,MA J X,GUO J,WANG J,ZHU M,CHEN Y,et al.Müller cell-derived VEGF is a significant contributor to retinal neovascularization[J].J Pathol,2009,219(4):446-454.
[62] LIU Y,SHEN J,FORTMANN S D,WANG J,VESTWEBER D,CAMPOCHIARO P A.Reversible retinal vessel closure from VEGF-induced leukocyte plugging[J].JCI Insight,2017,2(18):e95530.
[63] BRESSLER N M,BEAULIEU W T,GLASSMAN A R,BLINDER K J,BRESSLER S B,JAMPOL L M,et al.Persistent macular thickening following intravitreous aflibercept,bevacizumab,or ranibizumab for central-involved diabetic macular edema with vision impairment:a secondary analysis of a randomized clinical trial[J].JAMA Ophthalmol,2018,136(3):257-269.
[64] BROMBERG-WHITE J L,GLAZER L,DOWNER R,FURGE K,BOGUSLAWSKI E,DUESBERY N S.Identification of VEGF-independent cytokines in proliferative diabetic retinopathy vitreous[J].Invest Ophthalmol Vis Sci,2013,54(10):6472.
[65] VAN BERGEN T,ETIENNE I,CUNNINGHAM F,MOONS L,SCHLINGEMANN R O,FEYEN J H M,et al.The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases[J].Prog Retin Eye Res,2019,69:116-136.
[66] PERELMAN N,SELVARAJ S K,BATRA S,LUCK L R,ERDREICH-EPSTEIN A,COATES T D,et al.Placenta growth factor activates monocytes and correlates with sickle cell disease severity[J].Blood,2003,102(4):1506-1514.
[67] ANDO R,NODA K,NAMBA S,SAITO W,KANDA A,ISHIDA S.Aqueous humour levels of placental growth factor in diabetic retinopathy[J].Acta Ophthalmol,2014,92(3):e245-246.
[68] RANGASAMY S,MCGUIRE P G,FRANCO NITTA C,MONICKARAJ F,ORUGANTI S R,DAS A.Chemokine mediated monocyte trafficking into the retina:role of inflammation in alteration of the blood-retinal barrier in diabetic retinopathy[J].PLoS One,2014,9(10):e108508.
[69] GHARAEE-KERMANI M,DENHOLM E M,PHAN S H.Costimulation of fibroblast collagen and transforming growth factor β1 gene expression by monocyte chemoattractant protein-1 via specific receptors[J].J Biol Chem,1996,271(30):17779-17784.
[70] EL-ASRAR A M A,STRUYF S,KANGAVE D,GEBOES K,VAN DAMME J.Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy[J].Eur Cytokine Netw,2006,17(3):155-165.
[71] DONG N,LI X,XIAO L,YU W,WANG B,CHU L.Upregulation of retinal neuronal MCP-1 in the rodent model of diabetic retinopathy and its function in vitro[J].Invest Ophthalmol Vis Sci,2012,53(12):7567.
[72] DONG N,XU B,WANG B S,CHU L Q.Study of 27 aqueous humor cytokines in patients with type 2 diabetes with or without retinopathy[J].Mol Vis,2013,19:1734-1746.
[73] MITAMURA Y,TAKEUCHI S,MATSUDA A,TAGAWA Y,MIZUE Y,NISHIHIRA J.Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy[J].Ophthalmologica,2001,215(6):415-418.
[74] TASHIMO A,MITAMURA Y,NAGAI S,NAKAMURA Y,OHTSUKA K,MIZUE Y,et al.Aqueous levels of macrophage migration inhibitory factor and monocyte chemotactic protein-1 in patients with diabetic retinopathy[J].Diabet Med,2004,21(12):1292-1297.
[75] DEMIRCAN N,SAFRAN B G,SOYLU M,OZCAN A A,SIZMAZ S.Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy[J].Eye,2006,20(12):1366-1369.
[76] BEHL Y,KROTHAPALLI P,DESTA T,DIPIAZZA A,ROY S,GRAVES D T.Diabetes-enhanced tumor necrosis factor-α production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy[J].Am J Pathol,2008,172(5):1411-1418.
[77] HUANG H,GANDHI J K,ZHONG X,WEI Y,GONG J,DUH E J,et al.TNFalpha is required for late BRB breakdown in diabetic retinopathy,and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis[J].Invest Ophthalmol Vis Sci,2011,52(3):1336-1344.
[78] JOUSSEN A M,DOEHMEN S,LE M L,KOIZUMI K,RADETZKY S,KROHNE T U,et al.TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations[J].Mol Vis,2009,15:1418-1428.
[79] SUI A,CHEN X,SHEN J,DEMETRIADES A M,YAO Y,YAO Y,et al.Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1β/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model[J].Cell Death Dis,2020,11:901.
[80] VINCENT J A,MOHR S.Inhibition of caspase-1/interleukin-1β signaling prevents degeneration of retinal capillaries in diabetes and galactosemia[J].Diabetes,2007,56(1):224-230.
[81] YAO Y,LI R,DU J,LONG L,LI X,LUO N.Interleukin-6 and diabetic retinopathy:a systematic review and meta-analysis[J].Curr Eye Res,2019,44(5):564-574.
[82] SONODA S,SAKAMOTO T,SHIRASAWA M,YAMASHITA T,OTSUKA H,TERASAKI H.Correlation between reflectivity of subretinal fluid in OCT images and concentration of intravitreal VEGF in eyes with diabetic macular edema[J].Invest Ophthalmol Vis Sci,2013,54(8):5367.
[83] AUGUSTIN H G,YOUNG KOH G,THURSTON G,ALITALO K.Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system[J].Nat Rev Mol Cell Biol,2009,10(3):165-177.
[84] SCHOLZ A,PLATE K H,REISS Y.Angiopoietin-2:a multifaceted cytokine that functions in both angiogenesis and inflammation[J].Ann N Y Acad Sci,2015,1347(1):45-51.
[85] WYKOFF C C,ABREU F,ADAMIS A P,BASU K,EICHENBAUM D A,HASKOVA Z,et al.Efficacy,durability,and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE):two randomised,double-masked,phase 3 trials[J].Lancet,2022,399(10326):741-755.
[86] SHIRLEY M.Faricimab:first approval[J].Drugs,2022,82(7):825-830.
[87] ROSENBLATT A,UDAONDO P,CUNHA-VAZ J,SIVAPRASAD S,BANDELLO F,LANZETTA P,et al.A collaborative retrospective study on the efficacy and safety of intravitreal dexamethasone implant (ozurdex) in patients with diabetic macular edema:the European DME registry study[J].Ophthalmology,2020,127(3):377-393.
[88] TAMURA H,MIYAMOTO K,KIRYU J,MIYAHARA S,KATSUTA H,HIROSE F,et al.Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina[J].Invest Ophthalmol Vis Sci,2005,46(4):1440.
[89] BOYER D S,YOON Y H,BELFORT R,BANDELLO F,MATURI R K,AUGUSTIN A J,et al.Three-year,randomized,sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J].Ophthalmology,2014,121(10):1904-1914.
[90] CAMPOCHIARO P A,BROWN D M,PEARSON A,CHEN S,BOYER D,RUIZ-MORENO J,et al.Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema[J].Ophthalmology,2012,119(10):2125-2132.
[91] SADHUKHAN K,NASKAR S.Role of combined therapy of intravitreal ranibizumab and dexamethasone in refractory diabetic macular edema:a retrospective study[J].Maedica (Bucur),2021,16(4):615-619.
[92] BUSCH C,ZUR D,FRASER-BELL S,LANS I,SANTOS A R,LUPIDI M,et al.Shall we stay,or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema[J].Acta Diabetol,2018,55(8):789-796.
[93] YOLCU ,SOBACI G.The effect of combined treatment of bevacizumab and triamcinolone for diabetic macular edema refractory to previous intravitreal mono-injections[J].Int Ophthalmol,2015,35(1):73-79.
[94] KORENFELD M S,SILVERSTEIN S M,COOKE D L,VOGEL R,CROCKETT R S.Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain[J].J Cataract Refract Surg,2009,35(1):26-34.
[95] NAKANO S,YAMAMOTO T,KIRII E,ABE S,YAMASHITA H.Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema[J].Graefes Arch Clin Exp Ophthalmol,2010,248(6):805-810.
[96] KAUR S,YANGZES S,SINGH S,SACHDEV N.Efficacy and safety of topical difluprednate in persistent diabetic macular edema[J].Int Ophthalmol,2016,36(3):335-340.
[97] TANITO M,HARA K,TAKAI Y,MATSUOKA Y,NISHIMURA N,JANSOOK P,et al.Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema[J].Invest Ophthalmol Vis Sci,2011,52(11):7944-7948.
[98] OHIRA A,HARA K,JHANNESSON G,TANITO M,SGR-MSDTTIR G M,LUND S H,et al.Topical dexamethasone γ-cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema[J].Acta Ophthalmol,2015,93(7):610-615.
[99] DU Y,SARTHY V P,KERN T S.Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats[J].Am J Physiol Regul Integr Comp Physiol,2004,287(4):R735-R741.
[100] JONES J,FRANCIS P.Ophthalmic utility of topical bromfenac,a twice-daily nonsteroidal anti-inflammatory agent[J].Expert Opin Pharmacother,2009,10(14):2379-2385.
[101] GAYNES B.Topical ophthalmic NSAIDs:a discussion with focus on nepafenac ophthalmic suspension[J].Clin Ophthalmol,2008,2(2):355-368.
[102] PINNA A,BLASETTI F,RICCI G D,BOSCIA F.Bromfenac eyedrops in the treatment of diabetic macular edema:a pilot study[J].Eur J Ophthalmol,2017,27(3):326-330.
[103] CALLANAN D.Topical nepafenac in the treatment of diabetic macular edema[J].Clin Ophthalmol,2008,2(4):689-692.
[104] EVLIYAO〖KG-\*3〗G〖DD(-\*3/5〗ˇLU F,AKPOLAT ,KURT M M,EKI O,NURI ELIO〖KG-\*3〗G〖DD(-\*3/5〗ˇLU M.Retinal vascular caliber changes after topical nepafenac treatment for diabetic macular edema[J].Curr Eye Res,2018,43(3):357-361.
[105] HOWAIDY A,ELDALY Z H,ANIS M,OTHMAN T M.Prophylaxis of macular edema after cataract surgery in diabetic patients,topical Nepafenac versus intravitreal Ranibizumab[J].Eur J Ophthalmol,2022,32(1):205-212.
[106] NODA K,NAKAO S,ZANDI S,ENGELSTDTER V,MASHIMA Y,HAFEZI-MOGHADAM A.Vascular adhesion protein-1 regulates leukocyte transmigration rate in the retina during diabetes[J].Exp Eye Res,2009,89(5):774-781.
[107] SINGH A D,KULKARNI Y A.Vascular adhesion protein-1 and microvascular diabetic complications[J].Pharmacol Rep,2022,74(1):40-46.
[108] MURATA M,NODA K,FUKUHARA J,KANDA A,KASE S,SAITO W,et al.Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2012,53(7):4055.
[109] YOSHIKAWA N,NODA K,OZAWA Y,TSUBOTA K,MASHIMA Y,ISHIDA S.Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization[J].Mol Vis,2012,18:593-600.
[110] MATSUDA T,NODA K,MURATA M,KAWASAKI A,KANDA A,MASHIMA Y,et al.Vascular adhesion protein-1 blockade suppresses ocular inflammation after retinal laser photocoagulation in mice[J].Invest Ophthalmol Vis Sci,2017,58(7):3254.
[111] TKUS V,HORVTH  I,CSEK K,SZABADFI K,KOVCS-VALASEK A,DNYDI B,et al.Protective effects of the novel amine-oxidase inhibitor multi-target drug SZV 1287 on streptozotocin-induced beta cell damage and diabetic complications in rats[J].Biomed Pharmacother,2021,134:111105.
[112] NGUYEN Q D,SEPAH Y J,BERGER B,BROWN D, DO D V,GARCIA-HERNANDEZ A,et al.Primary outcomes of the VIDI study:phase 2,double-masked,randomized,active-controlled study of ASP8232 for diabetic macular edema[J].Int J Retina Vitr,2019,5:28.
[113] SCHILTER H C,COLLISON A,RUSSO R C,FOOT J S,YOW T T,VIEIRA A T,et al.Effects of an anti-inflammatory VAP-1/SSAO inhibitor,PXS-4728A,on pulmonary neutrophil migration[J].Respir Res,2015,16(1):1-14.
[114] MESQUIDA M,DRAWNEL F,LAIT P J,COPLAND D A,STIMPSON M L,LLOREN V,et al.Modelling macular edema:the effect of IL-6 and IL-6R blockade on human blood-retinal barrier integrity in vitro[J].Transl Vis Sci Technol,2019,8(5):32.
[115] BARNES T C,ANDERSON M E,MOOTS R J.The many faces of interleukin-6:the role of IL-6 in inflammation,vasculopathy,and fibrosis in systemic sclerosis[J].Int J Rheumatol,2011,2011:1-6.
[116] VALLE M L,DWORSHAK J,SHARMA A,IBRAHIM A S,AL-SHABRAWEY M,SHARMA S.Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells[J].Exp Eye Res,2019,178:27-36.
[117] SCHELLER J,CHALARIS A,SCHMIDT-ARRAS D,ROSE-JOHN S.The pro- and anti-inflammatory properties of the cytokine interleukin-6[J].Biochim Biophys Acta BBA Mol Cell Res,2011,1813(5):878-888.
[118] SHARMA S.Interleukin-6 trans-signaling:a pathway with therapeutic potential for diabetic retinopathy[J].Front Physiol,2021,12:689429.
[119] MITOMA H,HORIUCHI T,TSUKAMOTO H,UEDA N.Molecular mechanisms of action of anti-TNF-α agents:comparison among therapeutic TNF-α antagonists[J].Cytokine,2018,101:56-63.
[120] FENG S,YU H,YU Y,GENG Y,LI D,YANG C,et al.Levels of inflammatory cytokines IL-1β,IL-6,IL-8,IL-17A,and TNF-α in aqueous humour of patients with diabetic retinopathy[J].J Diabetes Res,2018,2018:8546423.
[121] STORTI F,PULLEY J,KUNER P,ABT M,LUHMANN U F O.Circulating biomarkers of inflammation and endothelial activation in diabetic retinopathy[J].Trans Vis Sci Tech,2021,10(12):8.
[122] SFIKAKIS P P,MARKOMICHELAKIS N,THEODOSSIADIS G P,GRIGOROPOULOS V,KATSILAMBROS N,THEODOSSIADIS P G.Regression of sight-threatening macular edema in type 2 diabetes following treatment with the anti-tumor necrosis factor monoclonal antibody infliximab[J].Diabetes Care,2005,28(2):445-447.
[123] GROTEGUT P,PIRVMAL N,KUEHN S,SMIT A,DICK H B,GRUS F H,et al.Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model[J].J Neuroinflammation,2020,17(1):375.
[124] YRJNHEIKKI J,TIKKA T,KEINNEN R,GOLDSTEINS G,CHAN P H,KOISTINAHO J.A tetracycline derivative,minocycline,reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window[J].Proc Natl Acad Sci USA,1999,96(23):13496-13500.
[125] KRADY J K,BASU A,ALLEN C M,XU Y,LANOUE K F,GARDNER T W,et al.Minocycline reduces proinflammatory cytokine expression,microglial activation,and caspase-3 activation in a rodent model of diabetic retinopathy[J].Diabetes,2005,54(5):1559-1565.
[126] CHEN M,ONA V O,LI M,FERRANTE R J,FINK K B,ZHU S,et al.Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease[J].Nat Med,2000,6(7):797-801.
[127] CUKRAS C A,PETROU P,CHEW E Y,MEYERLE C B,WONG W T.Oral minocycline for the treatment of diabetic macular edema (DME):results of a phase I/II clinical study[J].Invest Ophthalmol Vis Sci,2012,53(7):3865-3874.
[128] SHAW L T,MACKIN A,SHAH R,JAIN S,JAIN P,NAYAK R,et al.Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degene-ration and diabetic macular edema[J].Expert Opin Investig Drugs,2020,29(6):547-554.
[129] WILKINSON-BERKA J L,JONES D,TAYLOR G,JAWORSKI K,KELLY D J,LUDBROOK S B,et al.SB-267268,a nonpeptidic antagonist of αvβ3 and αvβ5Integrins,reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity[J].Invest Ophthalmol Vis Sci,2006,47(4):1600.
[130] MIRANDO A C,SHEN J,SILVA R L E,CHU Z,SASS N C,LORENC V E,et al.A collagen IV-derived peptide disrupts α5β1 integrin and potentiates Ang2/Tie2 signaling[J].JCI Insight,2019,4(4):e122043.
[131] ILIAKI E,POULAKI V,MITSIADES N,MITSIADES C S,MILLER J W,GRAGOUDAS E S.Role of α4 integrin (CD49d) in the pathogenesis of diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2009,50(10):4898.
[132] ZHANG W,LIU H,ROJAS M,CALDWELL R W,CALDWELL R B.Anti-inflammatory therapy for diabetic retinopathy[J].Immunotherapy,2011,3(5):609-628.
[133] FALAVARJANI K G,GOLABI S,MODARRES M.Intravitreal injection of methotrexate in persistent diabetic macular edema:a 6-month follow-up study[J].Graefes Arch Clin Exp Ophthalmol,2016,254(11):2159-2164.
[134] KRISHNADEV N,FOROOGHIAN F,CUKRAS C,WONG W,SALIGAN L,CHEW E Y,et al.Subconjunctival sirolimus in the treatment of diabetic macular edema[J].Graefes Arch Clin Exp Ophthalmol,2011,249(11):1627-1633.
[135] STAHEL M,BECKER M,GRAF N,MICHELS S.Systemic interleukin 1β inhibition in proliferative diabetic retinopathy[J].Retina,2016,36(2):385-391.
[136] GADEK T R,BURDICK D J,MCDOWELL R S,STANLEY M S,MARSTERS J C Jr,PARIS K J,et al.Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule[J].Science,2002,295(5557):1086-1089.
[137] RAO V R,PRESCOTT E,SHELKE N B,TRIVEDI R,THOMAS P,STRUBLE C,et al.Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR)[J].Invest Ophthalmol Vis Sci,2010,51(10):5198-5204.
[138] PASKOWITZ D M,NGUYEN Q D,GEHLBACH P,HANDA J T,SOLOMON S,STARK W,et al.Safety,tolerability,and bioavailability of topical SAR 1118,a novel antagonist of lymphocyte function-associated antigen-1:a phase 1b study[J].Eye,2012,26(7):944-949.
[139] NEBBIOSO M,LAMBIASE A,ARMENTANO M,TUCCIARONE G,SACCHETTI M,GRECO A,et al.Diabetic retinopathy,oxidative stress,and sirtuins:an in depth look in enzymatic patterns and new therapeutic horizons[J].Surv Ophthalmol,2022,67(1):168-183.

相似文献/References:

[1]杜玮 刘子扬 周艳艳 雒雷鸣.糖尿病视网膜病变与血清胆红素水平的关系[J].眼科新进展,2012,32(5):000.
[2]范松涛 卢建民.阿司匹林与糖尿病患者玻璃体出血以及玻璃体切割术疗效的相关性研究[J].眼科新进展,2012,32(11):000.
[3]李艳 李筱荣 袁佳琴 潘斌.糖尿病大鼠视网膜中VEGF、PEDF的表达与血-视网膜屏障损伤[J].眼科新进展,2013,33(1):000.
[4]李朝晖 崔治华 胡晓英 孟丽珠 张敬维.糖尿病视网膜病变激光面积与疗效的分析[J].眼科新进展,2013,33(2):000.
[5]冯冬梅 朱鸿 施彩虹.CXC趋化因子及其受体在糖尿病视网膜病变中的作用[J].眼科新进展,2013,33(6):000.
[6]牛淑玲.糖尿病视网膜病变患者HbAlc、FPG与血小板参数的变化及危险因素分析[J].眼科新进展,2013,33(7):000.
[7]毕春潮 王睿 王建洲 雷春灵 董晓娟 王小莉 薛晓辉.Ad-PEDF对糖尿病视网膜病变大鼠视网膜新生血管的抑制作用[J].眼科新进展,2013,33(8):000.
[8]杨萍 孙书明 李晓鹏.辛伐他汀对糖尿病视网膜病变和炎症因子的影响[J].眼科新进展,2013,33(8):000.
[9]罗文婷 孙大卫.血管黏附蛋白-1在眼科疾病中的研究进展[J].眼科新进展,2013,33(8):000.
[10]李小璐 马雅玲.糖尿病视网膜病变大鼠视网膜VEGF和PEDF的动态表达[J].眼科新进展,2013,33(9):000.
[11]兰文 陆燕 王春红 胡钦瑞 黄振平.糖尿病视网膜病变炎症的研究新进展[J].眼科新进展,2013,33(2):000.
[12]刘安琪,左中夫,吴传玲,等.Netrin-1对糖尿病视网膜病变大鼠的保护作用[J].眼科新进展,2020,40(1):011.[doi:10.13389/j.cnki.rao.2020.0003]
 LIU Anqi,ZUO Zhongfu,WU Chuanling,et al.Protective effect of Netrin-1 on rats with diabetic retinopathy[J].Recent Advances in Ophthalmology,2020,40(1):011.[doi:10.13389/j.cnki.rao.2020.0003]
[13]张凤俊,李晶明,刘秋平.糖尿病视网膜病变发病机制及潜在治疗研究进展[J].眼科新进展,2020,40(7):677.[doi:10.13389/j.cnki.rao.2020.0156]
 ZHANG Fengjun,LI Jingming,LIU Qiuping.Pathogenesis and potential treatment of diabetic retinopathy[J].Recent Advances in Ophthalmology,2020,40(1):677.[doi:10.13389/j.cnki.rao.2020.0156]
[14]唐磊,徐国彤,张敬法.褪黑素治疗糖尿病视网膜病变的研究进展[J].眼科新进展,2021,41(7):684.[doi:10.13389/j.cnki.rao.2021.0142]
 TANG Lei,XU Guotong,ZHANG Jingfa.Progress of melatonin in the treatment of diabetic retinopathy[J].Recent Advances in Ophthalmology,2021,41(1):684.[doi:10.13389/j.cnki.rao.2021.0142]
[15]孔慧,崔彦.CD40-ATP-P2X7/NLRP3炎症信号通路在糖尿病视网膜病变中的作用研究进展[J].眼科新进展,2021,41(9):879.[doi:10.13389/j.cnki.rao.2021.0184]
 KONG Hui,CUI Yan.Research progress of the CD40-ATP-P2X7/NLRP3 inflammatory pathway in diabetic retinopathy[J].Recent Advances in Ophthalmology,2021,41(1):879.[doi:10.13389/j.cnki.rao.2021.0184]
[16]司长峰,卜荔,徐楠,等.柴胡皂苷D对糖尿病视网膜病变大鼠的治疗作用[J].眼科新进展,2021,41(10):925.[doi:10.13389/j.cnki.rao.2021.0194]
 SI Changfeng,BU Li,XU Nan,et al.Therapeutical effect of Saikosaponin D on diabetic retinopathy of rats[J].Recent Advances in Ophthalmology,2021,41(1):925.[doi:10.13389/j.cnki.rao.2021.0194]
[17]孔慧,崔彦.糖尿病视网膜病变中视网膜内皮细胞功能障碍的研究进展[J].眼科新进展,2022,42(9):753.[doi:10.13389/j.cnki.rao.2022.0155]
 KONG Hui,CUI Yan.Research progress on retinal endothelial cell dysfunction in diabetic retinopathy[J].Recent Advances in Ophthalmology,2022,42(1):753.[doi:10.13389/j.cnki.rao.2022.0155]
[18]陈洪良,施健,娄雪莹,等.中性粒细胞胞外陷阱在糖尿病视网膜病变中作用的研究进展[J].眼科新进展,2023,43(9):747.[doi:10.13389/j.cnki.rao.2023.0150]
 CHEN Hongliang,SHI Jian,LOU Xueying,et al.Research progress on the effect of neutrophil extracellular traps in diabetic retinopathy[J].Recent Advances in Ophthalmology,2023,43(1):747.[doi:10.13389/j.cnki.rao.2023.0150]
[19]刘磊,刘珊珊,胡菲菲,等.吴茱萸碱调节cAMP/PKA信号通路在糖尿病大鼠视网膜损伤中的作用[J].眼科新进展,2024,44(2):094.[doi:10.13389/j.cnki.rao.2024.0019]
 LIU Lei,LIU Shanshan,HU Feifei,et al.Impact of evodiamine on retinal injury in diabetic rats by regulating cyclic adenosine monophosphate/protein kinase A signaling pathway[J].Recent Advances in Ophthalmology,2024,44(1):094.[doi:10.13389/j.cnki.rao.2024.0019]

备注/Memo

备注/Memo:
国家自然科学基金(编号:82171062)
更新日期/Last Update: 2024-01-05