Current progress on the study of microparticles in ocular fundus diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Song Yinting ,  Yan Hua

Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China;

Corresponding author：

Yan Hua, Email: phuayan2000@163.com

Keywords：

Cell-derived microparticles; Diabetic retinopathy; Macular degeneration; Retinoblastoma; Review

DOI：

10.3760/cma.j.issn.1005-1015.2018.02.025

Video：

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Abstract Full text Figures/Tables Video References Cited by

Microparticles are small vesicles that are released by budding of the plasma membrane during cellular activation and apoptotic cell breakdown. A spectrum of cell types can release microparticles including endothelial cells, platelets, macrophages, lymphocytes and tumor cells. Biological effects of microparticles mainly include procoagulant activity, inhibition of inflammation and cancer progression. The present study shows that vitreous microparticles isolated from proliferative diabetic retinopathy (PDR) stimulated endothelial cell proliferation and increased new vessel formation, promoting the pathological neovascularization in PDR patients. Oxidative stress induces the formation of retina pigment epithelium-derived microparticles carrying membrane complement regulatory proteins, which is associated with drusen formation and age related macular degeneration. Microparticles from lymphocyte (LMP) play an important role in anti-angiogenesis by altering the gene expression pattern of angiogenesis-related factors in macrophages. Besides, LMP are important proapoptotic regulators for retinoblastoma cells through reduction of spleen tyrosine kinase expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. However, how to apply the microparticles in the prevention and treatment of retinal diseases is a major challenge, because the study of the microparticles in the fundus diseases is still limited. Further studies conducted would certainly enhance the application of microparticles in the fundus diseases.

Citation： Song Yinting, Yan Hua. Current progress on the study of microparticles in ocular fundus diseases. Chinese Journal of Ocular Fundus Diseases, 2018, 34(2): 193-197. doi: 10.3760/cma.j.issn.1005-1015.2018.02.025 Copy

1.	Wolf P. The nature and significance of platelet products in human plasma[J]. Br J Haematol,1967, 13(3): 269-288.
2.	He Z, Tang Y, Qin C,et al. Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease[J]. Thromb Res,2017, 154: 19-25. DOI: 10.1016/j.thromres.2017.03.025.
3.	Shustova ON, Antonova OA, Golubeva NV, et al. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor[J]. Blood Coagul Fibrinolysis, 2017, 28(5): 373-382. DOI: 10.1097/MBC.0000000000000609.
4.	Dean WL, Lee MJ, Cummins TD, et al. Proteomic and functional characterisation of platelet microparticle size classes[J]. Thromb Haemost, 2009, 102(4): 711-718. DOI: 10.1160/TH09-04-243.
5.	György B, Szabó TG, Pásztói M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles[J]. Cell Mol Life Sci, 2011, 68(16): 2667-2688. DOI: 10.1007/s00018-011-0689-3.
6.	Tian Y, Salsbery B, Wang M, et al. Brain-derived microparticles induce systemic coagulation in a murine model of traumatic brain injury[J]. Blood, 2015, 125(13): 2151-2159. DOI: 10.1182/blood-2014-09-598805.
7.	Chahed S, Leroyer AS, Benzerroug M, et al. Increased vitreous shedding of microparticles in proliferative diabetic retinopathy stimulates endothelial proliferation[J]. Diabetes, 2010, 59(3): 694-701. DOI: 10.2337/db08-1524.
8.	Ogata N, Nomura S, Shouzu A, et al. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy[J]. Diabetes Res Clin Pract, 2006, 73(3): 241-248.
9.	Tumahai P, Saas P, Ricouard F, et al. Vitreous microparticle shedding in retinal detachment: a prospective comparative study[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 40-46. DOI: 10.1167/iovs.15-17446.
10.	Gelderman MP, Simak J. Flow cytometric analysis of cell membrane microparticles[J]. Methods Mol Biol, 2008, 484: 79-93. DOI: 10.1007/978-1-59745-398-1_6.
11.	Jimenez JJ, Jy W, Mauro LM, et al. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis[J]. Thromb Res, 2003, 109(4): 175-180.
12.	Distler JHW, Pisetsky DS, Huber LC, et al. Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases[J]. Arthritis Rheum, 2005, 52(11): 3337-3348.
13.	Beyer C, Pisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseases[J]. Nat Rev Rheumatol, 2010, 6(1): 21-29. DOI: 10.1038/nrrheum.2009.229.
14.	Mause SF, Weber C. Microparticles protagonists of a novel communication network for intercellular information exchange[J]. Circ Res, 2010, 107(9): 1047-1057. DOI: 10.1161/CIRCRESAHA.110.226456.
15.	Liu S, Wei L, Zhang Y, et al. Procoagulant activity and cellular origin of microparticles in human amniotic fluid[J]. Thromb Res, 2014, 133(4): 645-651. DOI: 10.1016/j.thromres.2013.12.043.
16.	Georgescu A, Alexandru N, Andrei E, et al. Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development[J]. Biol Cell, 2016, 108(8): 219-243. DOI: 10.1111/boc.201500104.
17.	Aung HH, Tung JP, Dean MM, et al. Procoagulant role of microparticles in routine storage of packed red blood cells: potential risk for prothrombotic post-transfusion complications[J]. Pathology, 2016, 49(1): 62-69. DOI: 10.1016/j.pathol.2016.10.001.
18.	Liu Y, He Z, Zhang Y, et al. Dissimilarity of increased phosphatidylserine-positive microparticles and associated coagulation activation in acute coronary syndromes[J]. Coron Artery Dis, 2016, 27(5): 365-375. DOI: 10.1097/MCA.0000000000000368.
19.	Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50-to 100-fold higher specific procoagulant activity than activated platelets[J]. Thromb Haemost, 2007, 97(3): 425-434.
20.	Chen VM, Ahamed J, Versteeg HH, et al. Evidence for activation of tissue factor by an allosteric disulfide bond[J]. Biochemistry, 2006, 45(39): 12020-12028.
21.	Holme PA, Solum NO, Brosstad F, et al. Microvesicles bind soluble fibrinogen, adhere to immobilized fibrinogen and coaggregate with platelets[J]. Thromb Haemost, 1998, 79(2): 389-394.
22.	Empana JP, Boulanger CM, Tafflet M, et al. Microparticles and sudden cardiac death due to coronary occlusion. The TIDE (Thrombus and Inflammation in sudden DEath) study[J]. Eur Heart J Acute Cardiovasc Care, 2015, 4(1): 28-36. DOI: 10.1177/2048872614538404.
23.	Sáenz-Cuesta M, Irizar H, Castillo-Triviño T, et al. Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis[J]. Biomark Med, 2014, 8(5): 653-661. DOI: 10.2217/bmm.14.9.
24.	Mallat Z, Hugel B, Ohan J, et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity[J]. Circulation, 1999, 99(3): 348-353.
25.	Guiducci S, Distler JH, Jungel A, et al. Elevated numbers of microparticles in the blood of patients with systemic sclerosis[J]. Arthritis Rheum, 2005, 52(2): 461-465.
26.	Nauta AJ, Trouw LA, Daha MR, et al. Direct binding of C1q to apoptotic cells and cell blebs induces complement activation[J]. Eur J Immunol, 2002, 32(6): 1726-1736.
27.	Distler JH, Huber LC, Gay S, et al. Microparticles as mediators of cellular cross-talk in inflammatory disease[J]. Autoimmunity, 2006, 39(8): 683-690.
28.	Saas P, Angelot F, Bardiaux L, et al. Phosphatidylserine-expressing cell by-products in transfusion: a pro-inflammatory or an anti-inflammatory effect?[J]. Transfus Clin Biol, 2012,19(3): 90-97. DOI: 10.1016/j.tracli.2012.02.002.
29.	Żmigrodzka M, Guzera M, Miśkiewicz A, et al. The biology of extracellular vesicles with focus on platelet microparticles and their role in cancer development and progression[J]. Tumour Biol, 2016, 37(11): 1-11. DOI: 10.1007/s13277-016-5358-6.
30.	Gong J, Jaiswal R, Dalla P, et al. Microparticles in cancer: a review of recent developments and the potential for clinical application[J]. Semin Cell Dev Biol, 2015, 40: 35-40. DOI: 10.1016/j.semcdb.2015.03.009.
31.	Poste G, Nicolson GL. Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells[J]. Proc Natl Acad Sci USA, 1980, 77(1): 399-403.
32.	Muralidharan-Chari V, Clancy JW, Sedgwick A, et al. Microvesicles: mediators of extracellular communication during cancer progression[J]. J Cell Sci, 2010, 123(10): 1603-1611. DOI: 10.1242/jcs.064386.
33.	Kowluru RA, Kowluru A, Mishra M, et al. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy[J]. Prog Retin Eye Res, 2015, 48(1-5): 40-61. DOI: 10.1016/j.preteyeres.2015.05.001.
34.	Curtis TM, Gardiner TA, Stitt AW. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?[J]. Eye, 2009, 23(7): 1496-1508. DOI: 10.1038/eye.2009.108.
35.	Stefánsson E. Ocular oxygenation and the treatment of diabetic retinopathy[J]. Surv Ophthalmol, 2006, 51(4): 364-380.
36.	Chen E, Park CH. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy[J]. Retina, 2006, 26(6): 699-700.
37.	Rangasamy S, McGuire PG, Franco Nitta C, et al. Chemokine mediated monocyte trafficking into the retina: role of inflammation in alteration of the bloodretinal barrier in diabetic retinopathy[J/OL]. PLoS One, 2014, 9(10): 108508[2014-10-20]. http://dx.plos.org/10.1371/journal.pone.0108508. DOI: 10.1371/journal.pone.0108508.
38.	Moschos MM, Pantazis P, Gatzioufas Z, et al. Association between platelet activating factor acetylhydrolase and diabetic retinopathy: does inflammation affect the retinal status?[J]. Prostaglandins Other Lipid Mediat, 2016, 122: 699-700. DOI: 10.1016/j.prostaglandins.2016.01.001.
39.	Mao H, Seo SJ, Biswal MR, et al. Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration[J]. Invest Ophthalmol Vis Sci, 2014, 55(7): 4613-4627. DOI: 10.1167/iovs.14-14633.
40.	Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration[J]. Nat Rev Immunol, 2013, 13(6): 438-451. DOI: 10.1038/nri3459.
41.	Rickman CB, Farsiu S, Toth CA, et al. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging[J]. Invest Ophthalmol Vis Sci, 2013, 54(14): 68-80. DOI: 10.1167/iovs.13-12757.
42.	Payne AJ, Kaja S, Naumchuk Y, et al. Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina[J]. Int J Mol Sci, 2014, 15(2): 1865-1886. DOI: 10.3390/ijms15021865.
43.	Carver KA, Yang D. N-Acetylcysteine amide protects against oxidative stress–induced microparticle release from human retinal pigment epithelial cells[J]. Invest Ophthalmol Vis Sci, 2016, 57(2): 360-371. DOI: 10.1167/iovs.15-17117.
44.	Carver KA, Lin CM, Bowes RC, et al. Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD[J]. Biochem Biophys Res Commun, 2016, 482(1): 81-86. DOI: 10.1016/j.bbrc.2016.10.140.
45.	Tahiri H, Omri S, Yang C, et al. Lymphocytic microparticles modulate angiogenic properties of macrophages in laser-induced choroidal neovascularization[J/OL]. Sci Rep, 2016, 6: 37391[2016-11-22]. http://dx.doi.org/10.1038/srep37391. DOI: 10.1038/srep37391.
46.	Murakami Y, Notomi S, Hisatomi T, et al. Photoreceptor cell death and rescue in retinal detachment and degenerations[J]. Prog Retin Eye Res, 2013, 37(12): 114-140. DOI: 10.1016/j.preteyeres.2013.08.001.
47.	Nakazawa T, Hisatomi T, Nakazawa C, et al. Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis[J]. Proc Natl Acad Sci USA, 2007, 104(7): 2425-2430.
48.	Aerts I, Lumbrosole RL, Gauthiervillars M, et al. Retinoblastoma update[J]. Arch Pediatr, 2016, 23(1): 112-116. DOI: 10.1016/j.arcped.2015.09.025.
49.	Qiu Q, Yang C, Wei X, et al. SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells[J]. Apoptosis, 2015, 5(12): 1-10. DOI: 10.1007/s10495-015-1177-2.
50.	Yang C, Xiong W, Qiu Q, et al. Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles[J]. Am J Physiol Regul Integr Comp Physiol, 2012, 302(8): 941-949. DOI: 10.1152/ajpregu.00527.2011.
51.	Mejía JC, Ortiz T, Tàssies D, et al. Procoagulant microparticles are increased in patients with Behçet’s disease but do not define a specific subset of clinical manifestations[J]. Clin Rheumatol, 2016, 35(3): 695-699. DOI: 10.1007/s10067-015-2903-4.
52.	Khan E, Ambrose NL, Ahnström J, et al. A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s syndrome[J/OL]. Sci Rep, 2016, 6: 38104[2016-012-07]. http://dx.doi.org/10.1038/srep38104. DOI: 10.1038/srep38104.

1. Wolf P. The nature and significance of platelet products in human plasma[J]. Br J Haematol,1967, 13(3): 269-288.
2. He Z, Tang Y, Qin C,et al. Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease[J]. Thromb Res,2017, 154: 19-25. DOI: 10.1016/j.thromres.2017.03.025.
3. Shustova ON, Antonova OA, Golubeva NV, et al. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor[J]. Blood Coagul Fibrinolysis, 2017, 28(5): 373-382. DOI: 10.1097/MBC.0000000000000609.
4. Dean WL, Lee MJ, Cummins TD, et al. Proteomic and functional characterisation of platelet microparticle size classes[J]. Thromb Haemost, 2009, 102(4): 711-718. DOI: 10.1160/TH09-04-243.
5. György B, Szabó TG, Pásztói M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles[J]. Cell Mol Life Sci, 2011, 68(16): 2667-2688. DOI: 10.1007/s00018-011-0689-3.
6. Tian Y, Salsbery B, Wang M, et al. Brain-derived microparticles induce systemic coagulation in a murine model of traumatic brain injury[J]. Blood, 2015, 125(13): 2151-2159. DOI: 10.1182/blood-2014-09-598805.
7. Chahed S, Leroyer AS, Benzerroug M, et al. Increased vitreous shedding of microparticles in proliferative diabetic retinopathy stimulates endothelial proliferation[J]. Diabetes, 2010, 59(3): 694-701. DOI: 10.2337/db08-1524.
8. Ogata N, Nomura S, Shouzu A, et al. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy[J]. Diabetes Res Clin Pract, 2006, 73(3): 241-248.
9. Tumahai P, Saas P, Ricouard F, et al. Vitreous microparticle shedding in retinal detachment: a prospective comparative study[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 40-46. DOI: 10.1167/iovs.15-17446.
10. Gelderman MP, Simak J. Flow cytometric analysis of cell membrane microparticles[J]. Methods Mol Biol, 2008, 484: 79-93. DOI: 10.1007/978-1-59745-398-1_6.
11. Jimenez JJ, Jy W, Mauro LM, et al. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis[J]. Thromb Res, 2003, 109(4): 175-180.
12. Distler JHW, Pisetsky DS, Huber LC, et al. Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases[J]. Arthritis Rheum, 2005, 52(11): 3337-3348.
13. Beyer C, Pisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseases[J]. Nat Rev Rheumatol, 2010, 6(1): 21-29. DOI: 10.1038/nrrheum.2009.229.
14. Mause SF, Weber C. Microparticles protagonists of a novel communication network for intercellular information exchange[J]. Circ Res, 2010, 107(9): 1047-1057. DOI: 10.1161/CIRCRESAHA.110.226456.
15. Liu S, Wei L, Zhang Y, et al. Procoagulant activity and cellular origin of microparticles in human amniotic fluid[J]. Thromb Res, 2014, 133(4): 645-651. DOI: 10.1016/j.thromres.2013.12.043.
16. Georgescu A, Alexandru N, Andrei E, et al. Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development[J]. Biol Cell, 2016, 108(8): 219-243. DOI: 10.1111/boc.201500104.
17. Aung HH, Tung JP, Dean MM, et al. Procoagulant role of microparticles in routine storage of packed red blood cells: potential risk for prothrombotic post-transfusion complications[J]. Pathology, 2016, 49(1): 62-69. DOI: 10.1016/j.pathol.2016.10.001.
18. Liu Y, He Z, Zhang Y, et al. Dissimilarity of increased phosphatidylserine-positive microparticles and associated coagulation activation in acute coronary syndromes[J]. Coron Artery Dis, 2016, 27(5): 365-375. DOI: 10.1097/MCA.0000000000000368.
19. Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50-to 100-fold higher specific procoagulant activity than activated platelets[J]. Thromb Haemost, 2007, 97(3): 425-434.
20. Chen VM, Ahamed J, Versteeg HH, et al. Evidence for activation of tissue factor by an allosteric disulfide bond[J]. Biochemistry, 2006, 45(39): 12020-12028.
21. Holme PA, Solum NO, Brosstad F, et al. Microvesicles bind soluble fibrinogen, adhere to immobilized fibrinogen and coaggregate with platelets[J]. Thromb Haemost, 1998, 79(2): 389-394.
22. Empana JP, Boulanger CM, Tafflet M, et al. Microparticles and sudden cardiac death due to coronary occlusion. The TIDE (Thrombus and Inflammation in sudden DEath) study[J]. Eur Heart J Acute Cardiovasc Care, 2015, 4(1): 28-36. DOI: 10.1177/2048872614538404.
23. Sáenz-Cuesta M, Irizar H, Castillo-Triviño T, et al. Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis[J]. Biomark Med, 2014, 8(5): 653-661. DOI: 10.2217/bmm.14.9.
24. Mallat Z, Hugel B, Ohan J, et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity[J]. Circulation, 1999, 99(3): 348-353.
25. Guiducci S, Distler JH, Jungel A, et al. Elevated numbers of microparticles in the blood of patients with systemic sclerosis[J]. Arthritis Rheum, 2005, 52(2): 461-465.
26. Nauta AJ, Trouw LA, Daha MR, et al. Direct binding of C1q to apoptotic cells and cell blebs induces complement activation[J]. Eur J Immunol, 2002, 32(6): 1726-1736.
27. Distler JH, Huber LC, Gay S, et al. Microparticles as mediators of cellular cross-talk in inflammatory disease[J]. Autoimmunity, 2006, 39(8): 683-690.
28. Saas P, Angelot F, Bardiaux L, et al. Phosphatidylserine-expressing cell by-products in transfusion: a pro-inflammatory or an anti-inflammatory effect?[J]. Transfus Clin Biol, 2012,19(3): 90-97. DOI: 10.1016/j.tracli.2012.02.002.
29. Żmigrodzka M, Guzera M, Miśkiewicz A, et al. The biology of extracellular vesicles with focus on platelet microparticles and their role in cancer development and progression[J]. Tumour Biol, 2016, 37(11): 1-11. DOI: 10.1007/s13277-016-5358-6.
30. Gong J, Jaiswal R, Dalla P, et al. Microparticles in cancer: a review of recent developments and the potential for clinical application[J]. Semin Cell Dev Biol, 2015, 40: 35-40. DOI: 10.1016/j.semcdb.2015.03.009.
31. Poste G, Nicolson GL. Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells[J]. Proc Natl Acad Sci USA, 1980, 77(1): 399-403.
32. Muralidharan-Chari V, Clancy JW, Sedgwick A, et al. Microvesicles: mediators of extracellular communication during cancer progression[J]. J Cell Sci, 2010, 123(10): 1603-1611. DOI: 10.1242/jcs.064386.
33. Kowluru RA, Kowluru A, Mishra M, et al. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy[J]. Prog Retin Eye Res, 2015, 48(1-5): 40-61. DOI: 10.1016/j.preteyeres.2015.05.001.
34. Curtis TM, Gardiner TA, Stitt AW. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?[J]. Eye, 2009, 23(7): 1496-1508. DOI: 10.1038/eye.2009.108.
35. Stefánsson E. Ocular oxygenation and the treatment of diabetic retinopathy[J]. Surv Ophthalmol, 2006, 51(4): 364-380.
36. Chen E, Park CH. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy[J]. Retina, 2006, 26(6): 699-700.
37. Rangasamy S, McGuire PG, Franco Nitta C, et al. Chemokine mediated monocyte trafficking into the retina: role of inflammation in alteration of the bloodretinal barrier in diabetic retinopathy[J/OL]. PLoS One, 2014, 9(10): 108508[2014-10-20]. http://dx.plos.org/10.1371/journal.pone.0108508. DOI: 10.1371/journal.pone.0108508.
38. Moschos MM, Pantazis P, Gatzioufas Z, et al. Association between platelet activating factor acetylhydrolase and diabetic retinopathy: does inflammation affect the retinal status?[J]. Prostaglandins Other Lipid Mediat, 2016, 122: 699-700. DOI: 10.1016/j.prostaglandins.2016.01.001.
39. Mao H, Seo SJ, Biswal MR, et al. Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration[J]. Invest Ophthalmol Vis Sci, 2014, 55(7): 4613-4627. DOI: 10.1167/iovs.14-14633.
40. Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration[J]. Nat Rev Immunol, 2013, 13(6): 438-451. DOI: 10.1038/nri3459.
41. Rickman CB, Farsiu S, Toth CA, et al. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging[J]. Invest Ophthalmol Vis Sci, 2013, 54(14): 68-80. DOI: 10.1167/iovs.13-12757.
42. Payne AJ, Kaja S, Naumchuk Y, et al. Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina[J]. Int J Mol Sci, 2014, 15(2): 1865-1886. DOI: 10.3390/ijms15021865.
43. Carver KA, Yang D. N-Acetylcysteine amide protects against oxidative stress–induced microparticle release from human retinal pigment epithelial cells[J]. Invest Ophthalmol Vis Sci, 2016, 57(2): 360-371. DOI: 10.1167/iovs.15-17117.
44. Carver KA, Lin CM, Bowes RC, et al. Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD[J]. Biochem Biophys Res Commun, 2016, 482(1): 81-86. DOI: 10.1016/j.bbrc.2016.10.140.
45. Tahiri H, Omri S, Yang C, et al. Lymphocytic microparticles modulate angiogenic properties of macrophages in laser-induced choroidal neovascularization[J/OL]. Sci Rep, 2016, 6: 37391[2016-11-22]. http://dx.doi.org/10.1038/srep37391. DOI: 10.1038/srep37391.
46. Murakami Y, Notomi S, Hisatomi T, et al. Photoreceptor cell death and rescue in retinal detachment and degenerations[J]. Prog Retin Eye Res, 2013, 37(12): 114-140. DOI: 10.1016/j.preteyeres.2013.08.001.
47. Nakazawa T, Hisatomi T, Nakazawa C, et al. Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis[J]. Proc Natl Acad Sci USA, 2007, 104(7): 2425-2430.
48. Aerts I, Lumbrosole RL, Gauthiervillars M, et al. Retinoblastoma update[J]. Arch Pediatr, 2016, 23(1): 112-116. DOI: 10.1016/j.arcped.2015.09.025.
49. Qiu Q, Yang C, Wei X, et al. SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells[J]. Apoptosis, 2015, 5(12): 1-10. DOI: 10.1007/s10495-015-1177-2.
50. Yang C, Xiong W, Qiu Q, et al. Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles[J]. Am J Physiol Regul Integr Comp Physiol, 2012, 302(8): 941-949. DOI: 10.1152/ajpregu.00527.2011.
51. Mejía JC, Ortiz T, Tàssies D, et al. Procoagulant microparticles are increased in patients with Behçet’s disease but do not define a specific subset of clinical manifestations[J]. Clin Rheumatol, 2016, 35(3): 695-699. DOI: 10.1007/s10067-015-2903-4.
52. Khan E, Ambrose NL, Ahnström J, et al. A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s syndrome[J/OL]. Sci Rep, 2016, 6: 38104[2016-012-07]. http://dx.doi.org/10.1038/srep38104. DOI: 10.1038/srep38104.

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