Dysregulation and activation of immune processes are important in age-related macular degeneration (AMD) pathogenesis. The single nucleotide polymorphism of complement factor H is widely recognized as a risk factor to AMD. Over-activation of nod-like receptor3 and polymorphism of Toll-Like Receptor 3 also associated with AMD. Except for innate immune processes, adaptive immunity also play a critical role in AMD, a growing body of evidence supports that auto-antibodies and T cells are related with AMD. Additionally A2E and lipid oxidation byproducts might also have a role in AMD pathogenesis.
Citation： MaYingxue, ChenSong. Dysregulation and activation of immune system in age-related macular degeneration pathogenesis. Chinese Journal of Ocular Fundus Diseases, 2016, 32(1): 100-103. doi: 10.3760/cma.j.issn.1005-1015.2016.01.028 Copy
| 1. | Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration[J]. Science,2005,308(5720):419-421. |
| 2. | Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration[J]. Science,2005,308(5720):385-389. |
| 3. | Clark SJ, Perveen R, Hakobyan S, et al. Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch's membrane in human retina[J]. J Biol Chem,2010,285(39):30192-30202.DOI: 10.1074/jbc.M110.103986. |
| 4. | Raychaudhuri S, Iartchouk O, Chin K, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration[J]. Nat Genet, 2011, 43 (12): 1232-1236.DOI: 10.1038/ng.976. |
| 5. | Weber BH, Charbel IP, Pauly D, et al. The role of the complement system in age-related macular degeneration[J]. Dtsch Arztebl Int,2014,111(8):133-138. DOI: 10.3238/arztebl.2014.0133. |
| 6. | Tuo J, Grob S, Zhang K, et al. Genetics of immunological and inflammatory components in age-related macular degeneration[J]. Ocul Immunol Inflamm, 2012, 20 (1):27-36.DOI:10.3109/09273948.2011.628432. |
| 7. | Clark SJ, Schmidt CQ, White AM, et al. Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration[J].J Immunol,2014,193(10):4962-4970.DOI:10.4049/jimmunol.1401613. |
| 8. | Clark SJ, Bishop PN. Role of factor h and related proteins in regulating complement activation in the macula, and relevance to age-related macular degeneration[J]. J Clin Med,2015,4(1):18-31.DOI: 10.3390/jcm4010018. |
| 9. | Fritsche LG, Lauer N, Hartmann A, et al. An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD)[J]. Hum Mol Genet,2010,19(23):4694-4704.DOI: 10.1093/hmg/ddq399. |
| 10. | Khandhadia S, Cipriani V, Yates JR, et al. Age-related macular degeneration and the complement system[J].Immunobiology,2012,217(2):127-146. DOI: 10.1016/j.imbio.2011.07.019. |
| 11. | Wang J, Ohno-Matsui K, Yoshida T, et al. Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen[J]. J Immunol,2008,181(1):712-720. |
| 12. | van de Ven JP, Nilsson SC, Tan PL, et al. A functional variant in the CFI gene confers a high risk of age-related macular degeneration[J]. Nat Genet, 2013, 45(7): 813-817.DOI: 10.1038/ng.2640. |
| 13. | Biasutto L, Chiechi A, Couch R, et al. Retinal pigment epithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidative stress[J]. Exp Cell Res,2013,319(13):2113-2123.DOI: 10.1016/j.yexcr.2013.05.005. |
| 14. | Wang AL, Lukas TJ, Yuan M, et al. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One,2009,4(1):4160. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612751/.DOI:10.1371/journal.pone.0004160. |
| 15. | Lachmann PJ. The amplification loop of the complement pathways[J]. Adv Immunol,2009,104:115-149.DOI:10.1016/S0065-2776(08)04004-2. |
| 16. | Hollyfield JG, Bonilha VL, Rayborn ME, et al. Oxidative damage-induced inflammation initiates age-related macular degeneration[J]. Nat Med,2008, 14(2): 194-198.DOI:10.1038/nm1709. |
| 17. | Dowling JK, O'Neill LA. Biochemical regulation of the inflammasome[J]. Crit Rev Biochem Mol Biol,2012,47(5):424-443.DOI: 10.3109/10409238.2012.694844. |
| 18. | Tseng WA, Thein T, Kinnunen K, et al. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration[J].Invest Ophthalmol Vis Sci,2013,54(1):110-120.DOI:10.1167/iovs.12-10655. |
| 19. | Mankan AK, Kubarenko A, Hornung V. Immunology in clinic review series; focus on autoinflammatory diseases: inflammasomes: mechanisms of activation[J].Clin Exp Immunol,2012,167(3):369-381.DOI: 10.1111/j.1365-2249.2011.04534.x. |
| 20. | Tarallo V, Hirano Y, Gelfand BD, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88[J]. Cell,2012,149(4):847-859.DOI: 10.1016/j.cell.2012.03.036. |
| 21. | Doyle SL, Campbell M, Ozaki E, et al. NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components[J]. Nat Med,2012,18(5):791-798.DOI:10.1038/nm.2717. |
| 22. | Liu RT, Gao J, Cao S, et al. Inflammatory mediators induced by amyloid-beta in the retina and RPE in vivo: implications for inflammasome activation in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2013, 54(3): 2225-2237.DOI:10.1167/iovs.12-10849. |
| 23. | Kauppinen A, Niskanen H, Suuronen T, et al. Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells--implications for age-related macular degeneration (AMD)[J]. Immunol Lett,2012,147(1-2):29-33. |
| 24. | Piippo N, Korkmaz A, Hytti M, et al. Decline in cellular clearance systems induces inflammasome signaling in human ARPE-19 cells[J]. Biochim Biophys Acta,2014,1843(12):3038-3046. |
| 25. | Lavalette S, Raoul W, Houssier M,et al.Interleukin-1βinhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration[J]. Am J Pathol,2011,178(5):2416-2423. DOI: 10.1016/j.ajpath.2011.01.013. |
| 26. | Campbell M, Doyle S, Humphries P. IL-18: a new player in immunotherapy for age-related macular degeneration?[J]. Expert Rev Clin Immunol, 2014, 10(10): 1273-1275.DOI: 10.1586/1744666X.2014.950231. |
| 27. | Kerur N, Hirano Y, Tarallo V, et al. TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3 inflammasome activation in geographic atrophy[J]. Invest Ophthalmol Vis Sci,2013,54(12):7395-7401.DOI: 10.1167/iovs.13-12500. |
| 28. | Kaneko H, Dridi S, Tarallo V, et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration[J]. Nature,2011,471(7338):325-330.DOI:10.1038/nature09830. |
| 29. | Cho Y, Wang JJ, Chew EY, et al. Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples[J]. Invest Ophthalmol Vis Sci,2009,50(12):5614-5618.DOI: 10.1167/iovs.09-3688. |
| 30. | Kleinman ME, Yamada K, Takeda A, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3[J]. Nature,2008,452(7187):591-597.DOI: 10.1038/nature06765. |
| 31. | Kleinman ME, Kaneko H, Cho WG, et al. Short-interfering RNAs induce retinal degeneration via TLR3 and IRF3[J]. Mol Ther,2012,20(1):101-108.DOI: 10.1038/mt.2011.212. |
| 32. | Shiose S, Chen Y, Okano K, et al. Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice[J]. J Biol Chem,2011,286(17):15543-15555.DOI: 10.1074/jbc.M111.228551. |
| 33. | West XZ, Malinin NL, Merkulova AA, et al. Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands[J].Nature,2010,467(7318):972-976.DOI:10.1038/nature09421. |
| 34. | Cherepanoff S, Mitchell P, Wang JJ, et al. Retinal autoantibody profile in early age-related macular degeneration: preliminary findings from the Blue Mountains Eye Study[J]. Clin Experiment Ophthalmol,2006,34(6):590-595. |
| 35. | Crabb JW, Miyagi M, Gu X, et al.Drusen proteome analysis: an approach to the etiology of age-related macular degeneration[J]. Proc Natl Acad Sci USA,2002, 99 (23):14682-14687. |
| 36. | Faber C, Singh A, Kruger FM, et al. Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood[J]. Ophthalmology,2013,120(11):2310-2316.DOI:10.1016/j.ophtha.2013.04.014. |
| 37. | Liu B, Wei L, Meyerle C, et al.Complement component C5a promotes expression of IL-22 and IL-17 from human T cells and its implication in age-related macular degeneration[J].J Transl Med,2011,9:1-12.DOI:10.1186/1479-5876-9-111. |
| 38. | Chen M, Muckersie E, Forrester JV, et al.Immune activation in retinal aging: a gene expression study[J]. Invest Ophthalmol Vis Sci,2010,51(11):5888-5896.DOI: 10.1167/iovs.09-5103. |
| 39. | Juel HB, Kaestel C, Folkersen L, et al. Retinal pigment epithelial cells upregulate expression of complement factors after co-culture with activated T cells[J]. Exp Eye Res,2011,92(3):180-188.DOI:10.1016/j.exer.2011.01.003. |
| 40. | Cruz-Guilloty F, Saeed AM, Duffort S, et al. T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration. PLoS One,2014,9(2):88201.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088201.DOI:10.1371/journal.pone.0088201. |
| 41. | Nussenblatt RB, Lee RW, Chew E, et al. Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention[J]. Am J Ophthalmol,2014,158(1):5-11.DOI:10.1016/j.ajo.2014.03.014. |
| 42. | Wei L, Liu B, Tuo J, et al. Hypomethylation of the IL17RC promoter associates with age-related macular degeneration[J].Cell Rep,2012,2(5):1151-1158.DOI:10.1016/j.celrep.2012.10.013. |
| 43. | Hasegawa E, Sonoda KH, Shichita T, et al. IL-23-independent induction of IL-17 from gammadelta T cells and innate lymphoid cells promotes experimental intraocular neovascularization[J]. J Immunol,2013,190(4):1778-1787.DOI: 10.4049/jimmunol.1202495. |
| 44. | Ryu S, Lee JH, Kim SI. IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes[J]. Clin Rheumatol, 2006, 25(1):16-20. |
| 45. | Anderson OA, Finkelstein A, Shima DT. A2E induces IL-1ss production in retinal pigment epithelial cells via the NLRP3 inflammasome. PLoS One, 2013, 8(6): 67263.http://discovery.ucl.ac.uk/1399286/1/journal.pone.0067263.pdf. DOI:10.1371/journal.pone.0067263. |
| 46. | Iriyama A, Inoue Y, Takahashi H, et al. A2E, a component of lipofuscin, is pro-angiogenic in vivo[J]. J Cell Physiol,2009,220(2):469-475.DOI: 10.1002/jcp.21792. |
| 47. | Radu RA, Hu J, Yuan Q, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration[J]. J Biol Chem,2011,286(21):18593-18601.DOI: 10.1074/jbc.M110.191866. |
| 48. | Catala A. Lipid peroxidation of membrane phospholipids in the vertebrate retina[J]. Front Biosci (Schol Ed),2011,3:52-60. |
| 49. | Krohne TU, Stratmann NK, Kopitz J, et al. Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells[J]. Exp Eye Res,2010,90(3):465-471.DOI: 10.1016/j.exer.2009.12.011. |
| 50. | Weismann D, Hartvigsen K, Lauer N, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress[J]. Nature, 2011, 478 (7367):76-81.DOI:10.1038/nature10449. |
| 51. | Sharma A, Sharma R, Chaudhary P, et al. 4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells[J]. Arch Biochem Biophys, 2008, 480 (2):85-94.DOI:10.1016/j.abb.2008.09.016. |
| 52. | Liu XC, Liu XF, Jian CX, et al. IL-33 is induced by amyloid-beta stimulation and regulates inflammatory cytokine production in retinal pigment epithelium cells[J]. Inflammation,2012,35(2):776-784. DOI: 10.1007/s10753-011-9379-4. |
| 53. | Kenney MC, Chwa M, Atilano SR, et al. Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration[J]. PLoS One,2013,8(1):54339. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054339. DOI: 10.1371/journal.pone.0054339. |
- 1. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration[J]. Science,2005,308(5720):419-421.
- 2. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration[J]. Science,2005,308(5720):385-389.
- 3. Clark SJ, Perveen R, Hakobyan S, et al. Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch's membrane in human retina[J]. J Biol Chem,2010,285(39):30192-30202.DOI: 10.1074/jbc.M110.103986.
- 4. Raychaudhuri S, Iartchouk O, Chin K, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration[J]. Nat Genet, 2011, 43 (12): 1232-1236.DOI: 10.1038/ng.976.
- 5. Weber BH, Charbel IP, Pauly D, et al. The role of the complement system in age-related macular degeneration[J]. Dtsch Arztebl Int,2014,111(8):133-138. DOI: 10.3238/arztebl.2014.0133.
- 6. Tuo J, Grob S, Zhang K, et al. Genetics of immunological and inflammatory components in age-related macular degeneration[J]. Ocul Immunol Inflamm, 2012, 20 (1):27-36.DOI:10.3109/09273948.2011.628432.
- 7. Clark SJ, Schmidt CQ, White AM, et al. Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration[J].J Immunol,2014,193(10):4962-4970.DOI:10.4049/jimmunol.1401613.
- 8. Clark SJ, Bishop PN. Role of factor h and related proteins in regulating complement activation in the macula, and relevance to age-related macular degeneration[J]. J Clin Med,2015,4(1):18-31.DOI: 10.3390/jcm4010018.
- 9. Fritsche LG, Lauer N, Hartmann A, et al. An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD)[J]. Hum Mol Genet,2010,19(23):4694-4704.DOI: 10.1093/hmg/ddq399.
- 10. Khandhadia S, Cipriani V, Yates JR, et al. Age-related macular degeneration and the complement system[J].Immunobiology,2012,217(2):127-146. DOI: 10.1016/j.imbio.2011.07.019.
- 11. Wang J, Ohno-Matsui K, Yoshida T, et al. Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen[J]. J Immunol,2008,181(1):712-720.
- 12. van de Ven JP, Nilsson SC, Tan PL, et al. A functional variant in the CFI gene confers a high risk of age-related macular degeneration[J]. Nat Genet, 2013, 45(7): 813-817.DOI: 10.1038/ng.2640.
- 13. Biasutto L, Chiechi A, Couch R, et al. Retinal pigment epithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidative stress[J]. Exp Cell Res,2013,319(13):2113-2123.DOI: 10.1016/j.yexcr.2013.05.005.
- 14. Wang AL, Lukas TJ, Yuan M, et al. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One,2009,4(1):4160. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612751/.DOI:10.1371/journal.pone.0004160.
- 15. Lachmann PJ. The amplification loop of the complement pathways[J]. Adv Immunol,2009,104:115-149.DOI:10.1016/S0065-2776(08)04004-2.
- 16. Hollyfield JG, Bonilha VL, Rayborn ME, et al. Oxidative damage-induced inflammation initiates age-related macular degeneration[J]. Nat Med,2008, 14(2): 194-198.DOI:10.1038/nm1709.
- 17. Dowling JK, O'Neill LA. Biochemical regulation of the inflammasome[J]. Crit Rev Biochem Mol Biol,2012,47(5):424-443.DOI: 10.3109/10409238.2012.694844.
- 18. Tseng WA, Thein T, Kinnunen K, et al. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration[J].Invest Ophthalmol Vis Sci,2013,54(1):110-120.DOI:10.1167/iovs.12-10655.
- 19. Mankan AK, Kubarenko A, Hornung V. Immunology in clinic review series; focus on autoinflammatory diseases: inflammasomes: mechanisms of activation[J].Clin Exp Immunol,2012,167(3):369-381.DOI: 10.1111/j.1365-2249.2011.04534.x.
- 20. Tarallo V, Hirano Y, Gelfand BD, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88[J]. Cell,2012,149(4):847-859.DOI: 10.1016/j.cell.2012.03.036.
- 21. Doyle SL, Campbell M, Ozaki E, et al. NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components[J]. Nat Med,2012,18(5):791-798.DOI:10.1038/nm.2717.
- 22. Liu RT, Gao J, Cao S, et al. Inflammatory mediators induced by amyloid-beta in the retina and RPE in vivo: implications for inflammasome activation in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2013, 54(3): 2225-2237.DOI:10.1167/iovs.12-10849.
- 23. Kauppinen A, Niskanen H, Suuronen T, et al. Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells--implications for age-related macular degeneration (AMD)[J]. Immunol Lett,2012,147(1-2):29-33.
- 24. Piippo N, Korkmaz A, Hytti M, et al. Decline in cellular clearance systems induces inflammasome signaling in human ARPE-19 cells[J]. Biochim Biophys Acta,2014,1843(12):3038-3046.
- 25. Lavalette S, Raoul W, Houssier M,et al.Interleukin-1βinhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration[J]. Am J Pathol,2011,178(5):2416-2423. DOI: 10.1016/j.ajpath.2011.01.013.
- 26. Campbell M, Doyle S, Humphries P. IL-18: a new player in immunotherapy for age-related macular degeneration?[J]. Expert Rev Clin Immunol, 2014, 10(10): 1273-1275.DOI: 10.1586/1744666X.2014.950231.
- 27. Kerur N, Hirano Y, Tarallo V, et al. TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3 inflammasome activation in geographic atrophy[J]. Invest Ophthalmol Vis Sci,2013,54(12):7395-7401.DOI: 10.1167/iovs.13-12500.
- 28. Kaneko H, Dridi S, Tarallo V, et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration[J]. Nature,2011,471(7338):325-330.DOI:10.1038/nature09830.
- 29. Cho Y, Wang JJ, Chew EY, et al. Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples[J]. Invest Ophthalmol Vis Sci,2009,50(12):5614-5618.DOI: 10.1167/iovs.09-3688.
- 30. Kleinman ME, Yamada K, Takeda A, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3[J]. Nature,2008,452(7187):591-597.DOI: 10.1038/nature06765.
- 31. Kleinman ME, Kaneko H, Cho WG, et al. Short-interfering RNAs induce retinal degeneration via TLR3 and IRF3[J]. Mol Ther,2012,20(1):101-108.DOI: 10.1038/mt.2011.212.
- 32. Shiose S, Chen Y, Okano K, et al. Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice[J]. J Biol Chem,2011,286(17):15543-15555.DOI: 10.1074/jbc.M111.228551.
- 33. West XZ, Malinin NL, Merkulova AA, et al. Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands[J].Nature,2010,467(7318):972-976.DOI:10.1038/nature09421.
- 34. Cherepanoff S, Mitchell P, Wang JJ, et al. Retinal autoantibody profile in early age-related macular degeneration: preliminary findings from the Blue Mountains Eye Study[J]. Clin Experiment Ophthalmol,2006,34(6):590-595.
- 35. Crabb JW, Miyagi M, Gu X, et al.Drusen proteome analysis: an approach to the etiology of age-related macular degeneration[J]. Proc Natl Acad Sci USA,2002, 99 (23):14682-14687.
- 36. Faber C, Singh A, Kruger FM, et al. Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood[J]. Ophthalmology,2013,120(11):2310-2316.DOI:10.1016/j.ophtha.2013.04.014.
- 37. Liu B, Wei L, Meyerle C, et al.Complement component C5a promotes expression of IL-22 and IL-17 from human T cells and its implication in age-related macular degeneration[J].J Transl Med,2011,9:1-12.DOI:10.1186/1479-5876-9-111.
- 38. Chen M, Muckersie E, Forrester JV, et al.Immune activation in retinal aging: a gene expression study[J]. Invest Ophthalmol Vis Sci,2010,51(11):5888-5896.DOI: 10.1167/iovs.09-5103.
- 39. Juel HB, Kaestel C, Folkersen L, et al. Retinal pigment epithelial cells upregulate expression of complement factors after co-culture with activated T cells[J]. Exp Eye Res,2011,92(3):180-188.DOI:10.1016/j.exer.2011.01.003.
- 40. Cruz-Guilloty F, Saeed AM, Duffort S, et al. T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration. PLoS One,2014,9(2):88201.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088201.DOI:10.1371/journal.pone.0088201.
- 41. Nussenblatt RB, Lee RW, Chew E, et al. Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention[J]. Am J Ophthalmol,2014,158(1):5-11.DOI:10.1016/j.ajo.2014.03.014.
- 42. Wei L, Liu B, Tuo J, et al. Hypomethylation of the IL17RC promoter associates with age-related macular degeneration[J].Cell Rep,2012,2(5):1151-1158.DOI:10.1016/j.celrep.2012.10.013.
- 43. Hasegawa E, Sonoda KH, Shichita T, et al. IL-23-independent induction of IL-17 from gammadelta T cells and innate lymphoid cells promotes experimental intraocular neovascularization[J]. J Immunol,2013,190(4):1778-1787.DOI: 10.4049/jimmunol.1202495.
- 44. Ryu S, Lee JH, Kim SI. IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes[J]. Clin Rheumatol, 2006, 25(1):16-20.
- 45. Anderson OA, Finkelstein A, Shima DT. A2E induces IL-1ss production in retinal pigment epithelial cells via the NLRP3 inflammasome. PLoS One, 2013, 8(6): 67263.http://discovery.ucl.ac.uk/1399286/1/journal.pone.0067263.pdf. DOI:10.1371/journal.pone.0067263.
- 46. Iriyama A, Inoue Y, Takahashi H, et al. A2E, a component of lipofuscin, is pro-angiogenic in vivo[J]. J Cell Physiol,2009,220(2):469-475.DOI: 10.1002/jcp.21792.
- 47. Radu RA, Hu J, Yuan Q, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration[J]. J Biol Chem,2011,286(21):18593-18601.DOI: 10.1074/jbc.M110.191866.
- 48. Catala A. Lipid peroxidation of membrane phospholipids in the vertebrate retina[J]. Front Biosci (Schol Ed),2011,3:52-60.
- 49. Krohne TU, Stratmann NK, Kopitz J, et al. Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells[J]. Exp Eye Res,2010,90(3):465-471.DOI: 10.1016/j.exer.2009.12.011.
- 50. Weismann D, Hartvigsen K, Lauer N, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress[J]. Nature, 2011, 478 (7367):76-81.DOI:10.1038/nature10449.
- 51. Sharma A, Sharma R, Chaudhary P, et al. 4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells[J]. Arch Biochem Biophys, 2008, 480 (2):85-94.DOI:10.1016/j.abb.2008.09.016.
- 52. Liu XC, Liu XF, Jian CX, et al. IL-33 is induced by amyloid-beta stimulation and regulates inflammatory cytokine production in retinal pigment epithelium cells[J]. Inflammation,2012,35(2):776-784. DOI: 10.1007/s10753-011-9379-4.
- 53. Kenney MC, Chwa M, Atilano SR, et al. Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration[J]. PLoS One,2013,8(1):54339. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054339. DOI: 10.1371/journal.pone.0054339.