Streilein JW. Regional immunity and ocular immune privilege. Chem Immunol. 1999;73:11–38.

PubMed  CAS  Google Scholar 

Streilein JW. Immunoregulatory mechanisms of the eye. Prog Retin Eye Res. 1999;18(3):357–70.

Article  PubMed  CAS  Google Scholar 

Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol. 2003;3(11):879–89.

Article  PubMed  CAS  Google Scholar 

Shechter R, London A, Schwartz M. Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat Rev Immunol. 2013;13(3):206–18.

Article  PubMed  CAS  Google Scholar 

Strauss O. Pharmacology of the retinal pigment epithelium, the interface between retina and body system. Eur J Pharmacol. 2016;787:84–93.

Article  PubMed  CAS  Google Scholar 

Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85(3):845–81.

Article  PubMed  CAS  Google Scholar 

Lakkaraju A, Umapathy A, Tan LX, Daniele L, Philp NJ, Boesze-Battaglia K, et al. The cell biology of the retinal pigment epithelium. Prog Retin Eye Res. 2020;78:100846.

Article  Google Scholar 

Sparrow JR, Hicks D, Hamel CP. The retinal pigment epithelium in health and disease. Curr Mol Med. 2010;10(9):802–23.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Camelo S, Calippe B, Lavalette S, Dominguez E, Hur J, Devevre E, et al. Thinning of the RPE and choroid associated with T lymphocyte recruitment in aged and light-challenged mice. Mol Vis. 2015;21:1051–9.

PubMed  PubMed Central  CAS  Google Scholar 

Housset M, Sennlaub F. Thrombospondin-1 and pathogenesis of age-related macular degeneration. J Ocul Pharmacol Ther. 2015;31(7):406–12.

Article  PubMed  CAS  Google Scholar 

Levy O, Calippe B, Lavalette S, Hu SJ, Raoul W, Dominguez E, et al. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration. EMBO Mol Med. 2015;7(2):211–26.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mathis T, Housset M, Eandi C, Beguier F, Touhami S, Reichman S, et al. Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNF-alpha. Aging Cell. 2017;16(1):173–82.

Article  PubMed  CAS  Google Scholar 

Omri S, Behar-Cohen F, de Kozak Y, Sennlaub F, Verissimo LM, Jonet L, et al. Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCzeta in the Goto Kakizaki rat model. Am J Pathol. 2011;179(2):942–53.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Touhami S, Beguier F, Augustin S, Charles-Messance H, Vignaud L, Nandrot EF, et al. Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation. J Neuroinflammation. 2018;15(1):85.

Article  PubMed  PubMed Central  Google Scholar 

Sennlaub F, Auvynet C, Calippe B, Lavalette S, Poupel L, Hu SJ, et al. CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice. EMBO Mol Med. 2013;5(11):1775–93.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Busch C, Annamalai B, Abdusalamova K, Reichhart N, Huber C, Lin Y, et al. Anaphylatoxins Activate Ca(2+), Akt/PI3-Kinase, and FOXO1/FoxP3 in the Retinal Pigment Epithelium. Front Immunol. 2017;8:703.

Article  PubMed  PubMed Central  Google Scholar 

Brandstetter C, Holz FG, Krohne TU. Complement Component C5a primes retinal pigment epithelial cells for inflammasome activation by lipofuscin-mediated photooxidative damage. J Biol Chem. 2015;290(52):31189–98.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fernandez-Godino R, Garland DL, Pierce EA. A local complement response by RPE causes early-stage macular degeneration. Hum Mol Genet. 2015;24(19):5555–69.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fernandez-Godino R, Pierce EA. C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway. Sci Rep. 2018;8(1):9679.

Article  PubMed  PubMed Central  Google Scholar 

Hu M, Liu B, Jawad S, Ling D, Casady M, Wei L, et al. C5a contributes to intraocular inflammation by affecting retinal pigment epithelial cells and immune cells. Br J Ophthalmol. 2011;95(12):1738–44.

Article  PubMed  Google Scholar 

Long Q, Cao X, Bian A, Li Y. C3a Increases VEGF and Decreases PEDF mRNA levels in human retinal pigment epithelial cells. Biomed Res Int. 2016;2016:6958752.

Article  PubMed  PubMed Central  Google Scholar 

Ramos de Carvalho JE, Klaassen I, Vogels IM, Schipper-Krom S, van Noorden CJ, Reits E, et al. Complement factor C3a alters proteasome function in human RPE cells and in an animal model of age-related RPE degeneration. Invest Ophthalmol Vis Sci. 2013;54(10):6489–501.

Article  PubMed  CAS  Google Scholar 

Schafer N, Grosche A, Schmitt SI, Braunger BM, Pauly D. Complement components showed a time-dependent local expression pattern in constant and acute white light-induced photoreceptor damage. Front Mol Neurosci. 2017;10:197.

Article  PubMed  PubMed Central  Google Scholar 

Skeie JM, Fingert JH, Russell SR, Stone EM, Mullins RF. Complement component C5a activates ICAM-1 expression on human choroidal endothelial cells. Invest Ophthalmol Vis Sci. 2010;51(10):5336–42.

Article  PubMed  PubMed Central  Google Scholar 

Vogt SD, Barnum SR, Curcio CA, Read RW. Distribution of complement anaphylatoxin receptors and membrane-bound regulators in normal human retina. Exp Eye Res. 2006;83(4):834–40.

Article  PubMed  CAS  Google Scholar 

Wang YP, Hui YN, Wang YS, Wang HY. Detection of C5a receptor expressions on human epiretinal membranes and cultured RPE cells by immunohistochemical staining. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2003;19(3):221–2.

PubMed  CAS  Google Scholar 

Dietrich L, Lucius R, Roider J, Klettner A. Interaction of inflammatorily activated retinal pigment epithelium with retinal microglia and neuronal cells. Exp Eye Res. 2020;199: 108167.

Article  PubMed  CAS  Google Scholar 

Klettner A, Hamann T, Schluter K, Lucius R, Roider J. Retinal pigment epithelium cells alter the pro-inflammatory response of retinal microglia to TLR-3 stimulation. Acta Ophthalmol. 2014;92(8):e621–9.

Article  PubMed  CAS  Google Scholar 

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(1–2):7–15.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Tarallo V, Hirano Y, Gelfand BD, Dridi S, Kerur N, Kim Y, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell. 2012;149(4):847–59.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Terheyden L, Roider J, Klettner A. Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro. Graefes Arch Clin Exp Ophthalmol. 2021;259(2):413–24.

Article  PubMed  CAS  Google Scholar 

Zhu Y, Dai B, Li Y, Peng H. C5a and toll-like receptor 4 crosstalk in retinal pigment epithelial cells. Mol Vis. 2015;21:1122–9.

PubMed  PubMed Central  CAS  Google Scholar 

Sun Q, Gong L, Qi R, Qing W, Zou M, Ke Q, et al. Oxidative stress-induced KLF4 activates inflammatory response through IL17RA and its downstream targets in retinal pigment epithelial cells. Free Radic Biol Med. 2020;147:271–81.

Article  PubMed  CAS  Google Scholar 

Zhang J, Bai Y, Huang L, Qi Y, Zhang Q, Li S, et al. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration. Cell Death Dis. 2015;6: e1972.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zamiri P, Masli S, Streilein JW, Taylor AW. Pigment epithelial growth factor suppresses inflammation by modulating macrophage activation. Invest Ophthalmol Vis Sci. 2006;47(9):3912–8.

Article  PubMed  Google Scholar 

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): e67263.