Functional role of translocator protein and its ligands in ocular diseases (Review)
- Authors:
- Mingyi Yu
- Shaozhen Zhao
-
Affiliations: Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 30384, P.R. China, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 30384, P.R. China - Published online on: January 8, 2024 https://doi.org/10.3892/mmr.2024.13157
- Article Number: 33
-
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
|
Shoshan-Barmatz V, Pittala S and Mizrachi D: VDAC1 and the TSPO: Expression, Interactions, and associated functions in health and disease states. Int J Mol Sci. 20:33482019. View Article : Google Scholar : PubMed/NCBI | |
|
Braestrup C and Squires RF: Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci USA. 74:3805–3809. 1977. View Article : Google Scholar : PubMed/NCBI | |
|
Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapère JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang MR and Gavish M: Translocator protein (18kDa): New nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 27:402–409. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Tu LN, Zhao AH, Hussein M, Stocco DM and Selvaraj V: Translocator Protein (TSPO) affects mitochondrial fatty acid oxidation in steroidogenic cells. Endocrinology. 157:1110–1121. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Bonsack F and Sukumari-Ramesh S: TSPO: An evolutionarily conserved protein with elusive functions. Int J Mol Sci. 19:16942018. View Article : Google Scholar : PubMed/NCBI | |
|
Fan J and Papadopoulos V: Mitochondrial TSPO deficiency triggers retrograde signaling in MA-10 mouse tumor leydig cells. Int J Mol Sci. 22:2522020. View Article : Google Scholar : PubMed/NCBI | |
|
Vainshtein A, Veenman L, Shterenberg A, Singh S, Masarwa A, Dutta B, Island B, Tsoglin E, Levin E, Leschiner S, et al: Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease. Cell Death Discov. 1:150272015. View Article : Google Scholar : PubMed/NCBI | |
|
Sileikyte J, Blachly-Dyson E, Sewell R, Carpi A, Menabò R, Di Lisa F, Ricchelli F, Bernardi P and Forte M: Regulation of the mitochondrial permeability transition pore by the outer membrane does not involve the peripheral benzodiazepine receptor (Translocator Protein of 18 kDa (TSPO)). J Biol Chem. 289:13769–13781. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Ilkan Z and Akar FG: The mitochondrial translocator protein and the emerging link between oxidative stress and arrhythmias in the diabetic heart. Front Physiol. 9:15182018. View Article : Google Scholar : PubMed/NCBI | |
|
Arbo BD, Ribeiro MF and Garcia-Segura LM: Development of new treatments for Alzheimer's disease based on the modulation of translocator protein (TSPO). Ageing Res Rev. 54:1009432019. View Article : Google Scholar : PubMed/NCBI | |
|
Mitro N, Cermenati G, Giatti S, Abbiati F, Pesaresi M, Calabrese D, Garcia-Segura LM, Caruso D and Melcangi RC: LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals. Neurochem Int. 60:616–621. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Veenman L and Gavish M: The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development. Pharmacol Ther. 110:503–524. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Barron AM, Garcia-Segura LM, Caruso D, Jayaraman A, Lee JW, Melcangi RC and Pike CJ: Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease. J Neurosci. 33:8891–8897. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Daugherty DJ, Selvaraj V, Chechneva OV, Liu XB, Pleasure DE and Deng W: A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol Med. 5:891–903. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wu LP, Gong ZF, Wang H, Zhou ZS, Zhang MM, Liu C, Ren HM, Yang J, Han Y and Zeng CY: TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation. Acta Pharmacol Sin. 41:34–46. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wang M, Wang X, Zhao L, Ma W, Rodriguez IR, Fariss RN and Wong WT: Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. J Neurosci. 34:3793–3806. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Biswas L, Zhou X, Dhillon B, Graham A and Shu X: Retinal pigment epithelium cholesterol efflux mediated by the 18 kDa translocator protein, TSPO, a potential target for treating age-related macular degeneration. Hum Mol Genet. 26:4327–4339. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Mages K, Grassmann F, Jagle H, Rupprecht R, Weber BHF, Hauck SM and Grosche A: The agonistic TSPO ligand XBD173 attenuates the glial response thereby protecting inner retinal neurons in a murine model of retinal ischemia. J Neuroinflammation. 16:432019. View Article : Google Scholar : PubMed/NCBI | |
|
Guo Y, Sun Z, Wang L, Jiang R, Shu Q and Xu G: Increased expression of TSPO-VDAC complex is correlated with NLRP3 inflammasome activation in diabetic retinopathy. Mol Med Rep. 26:3532022. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Y, Ou Y, Ju Z, Zhang X, Zheng L, Li J, Sun Y and Liu X: Visualization of translocator protein (18 kDa) (TSPO) in the retina of diabetic retinopathy rats using fluorine-18-DPA-714. Ann Nucl Med. 34:675–681. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lacapere JJ, Duma L, Finet S, Kassiou M and Papadopoulos V: Insight into the Structural Features of TSPO: Implications for drug development. Trends Pharmacol Sci. 41:110–122. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Papadopoulos V, Aghazadeh Y, Fan J, Campioli E, Zirkin B and Midzak A: Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis. Mol Cell Endocrinol. 408:90–98. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Jaremko M, Jaremko L, Jaipuria G, Becker S and Zweckstetter M: Structure of the mammalian TSPO/PBR protein. Biochem Soc Trans. 43:566–571. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, Groyer G, Adams D and Schumacher M: Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov. 9:971–988. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Biswas L, Farhan F, Reilly J, Bartholomew C and Shu X: TSPO ligands promote cholesterol efflux and suppress oxidative stress and inflammation in choroidal endothelial cells. Int J Mol Sci. 19:37402018. View Article : Google Scholar : PubMed/NCBI | |
|
Jaremko L, Jaremko M, Giller K, Becker S and Zweckstetter M: Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science. 343:1363–1366. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Morohaku K, Pelton SH, Daugherty DJ, Butler WR, Deng W and Selvaraj V: Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology. 155:89–97. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Tu LN, Morohaku K, Manna PR, Pelton SH, Butler WR, Stocco DM and Selvaraj V: Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. J Biol Chem. 289:27444–27454. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Tu LN, Zhao AH, Stocco DM and Selvaraj V: PK11195 effect on steroidogenesis is not mediated through the translocator protein (TSPO). Endocrinology. 156:1033–1039. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao AH, Tu LN, Mukai C, Sirivelu MP, Pillai VV, Morohaku K, Cohen R and Selvaraj V: Mitochondrial translocator protein (TSPO) function is not essential for heme biosynthesis. J Biol Chem. 291:1591–1603. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Casellas P, Galiegue S and Basile AS: Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 40:475–486. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Corsi L, Geminiani E and Baraldi M: Peripheral benzodiazepine receptor (PBR) new insight in cell proliferation and cell differentiation review. Curr Clin Pharmacol. 3:38–45. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Gatliff J, East D, Crosby J, Abeti R, Harvey R, Craigen W, Parker P and Campanella M: TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy. 10:2279–2296. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Varga B, Marko K, Hadinger N, Jelitai M, Demeter K, Tihanyi K, Vas A and Madarász E: Translocator protein (TSPO 18kDa) is expressed by neural stem and neuronal precursor cells. Neurosci Lett. 462:257–262. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Veenman L and Gavish M: The role of 18 kDa mitochondrial translocator protein (TSPO) in programmed cell death, and effects of steroids on TSPO expression. Curr Mol Med. 12:398–412. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Bernardi P, Carraro M and Lippe G: The mitochondrial permeability transition: Recent progress and open questions. FEBS J. 289:7051–7074. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Loth MK, Guariglia SR, Re DB, Perez J, de Paiva VN, Dziedzic JL, Chambers JW, Azzam DJ and Guilarte TR: A novel interaction of translocator protein 18 kDa (TSPO) with NADPH oxidase in microglia. Mol Neurobiol. 57:4467–4487. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Gatliff J, East DA, Singh A, Alvarez MS, Frison M, Matic I, Ferraina C, Sampson N, Turkheimer F and Campanella M: A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling. Cell Death Dis. 8:e28962017. View Article : Google Scholar : PubMed/NCBI | |
|
Zeno S, Veenman L, Katz Y, Bode J, Gavish M and Zaaroor M: The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of protoporphyrin IX. Involvement of reactive oxygen species (ROS). Curr Mol Med. 12:494–501. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wolf A, Herb M, Schramm M and Langmann T: The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye. Nat Commun. 11:27092020. View Article : Google Scholar : PubMed/NCBI | |
|
Rupprecht R, Rammes G, Eser D, Baghai TC, Schüle C, Nothdurfter C, Troxler T, Gentsch C, Kalkman HO, Chaperon F, et al: Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science. 325:490–493. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Barresi E, Robello M, Costa B, Da Pozzo E, Baglini E, Salerno S, Da Settimo F, Martini C and Taliani S: An update into the medicinal chemistry of translocator protein (TSPO) ligands. Eur J Med Chem. 209:1129242021. View Article : Google Scholar : PubMed/NCBI | |
|
Gut P: Targeting mitochondrial energy metabolism with TSPO ligands. Biochem Soc Trans. 43:537–542. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Taketani S, Kohno H, Furukawa T and Tokunaga R: Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. J Biochem. 117:875–880. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Snyder SH, Verma A and Trifiletti RR: The peripheral-type benzodiazepine receptor: A protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands. FASEB J. 1:282–288. 1987. View Article : Google Scholar : PubMed/NCBI | |
|
Veenman L, Vainshtein A, Yasin N, Azrad M and Gavish M: Tetrapyrroles as endogenous TSPO ligands in eukaryotes and prokaryotes: Comparisons with synthetic ligands. Int J Mol Sci. 17:8802016. View Article : Google Scholar : PubMed/NCBI | |
|
Tonon MC, Vaudry H, Chuquet J, Guillebaud F, Fan J, Masmoudi-Kouki O, Vaudry D, Lanfray D, Morin F, Prevot V, et al: Endozepines and their receptors: Structure, functions and pathophysiological significance. Pharmacol Ther. 208:1073862020. View Article : Google Scholar : PubMed/NCBI | |
|
Ma Z, An R, Chen M, Wang X and Zhu M: Random versus Block Glycopolymers bearing betulin and porphyrin for enhanced photodynamic therapy. Biomacromolecules. 23:5074–5083. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Yamamoto M, Arimura H, Fukushige T, Minami K, Nishizawa Y, Tanimoto A, Kanekura T, Nakagawa M, Akiyama S and Furukawa T: Abcb10 role in heme biosynthesis in vivo: Abcb10 knockout in mice causes anemia with protoporphyrin IX and iron accumulation. Mol Cell Biol. 34:1077–1084. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Batoko H, Veljanovski V and Jurkiewicz P: Enigmatic Translocator protein (TSPO) and cellular stress regulation. Trends Biochem Sci. 40:497–503. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Korolnek T and Hamza I: Like iron in the blood of the people: The requirement for heme trafficking in iron metabolism. Front Pharmacol. 5:1262014. View Article : Google Scholar : PubMed/NCBI | |
|
Chauveau F, Boutin H, Van Camp N, Dolle F and Tavitian B: Nuclear imaging of neuroinflammation: A comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 35:2304–2319. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Dolle F, Luus C, Reynolds A and Kassiou M: Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem. 16:2899–2923. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Fan Z, Calsolaro V, Atkinson RA, Femminella GD, Waldman A, Buckley C, Trigg W, Brooks DJ, Hinz R and Edison P: Flutriciclamide (18F-GE180) PET: First-in-Human PET study of novel third-generation in vivo marker of human translocator protein. J Nucl Med. 57:1753–1759. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Chiabrando D, Marro S, Mercurio S, Giorgi C, Petrillo S, Vinchi F, Fiorito V, Fagoonee S, Camporeale A, Turco E, et al: The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation. J Clin Invest. 122:4569–4579. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ni R, Rojdner J, Voytenko L, Dyrks T, Thiele A, Marutle A and Nordberg A: In vitro characterization of the regional binding distribution of amyloid PET tracer florbetaben and the glia tracers deprenyl and PK11195 in Autopsy Alzheimer's brain tissue. J Alzheimers Dis. 80:1723–1737. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ishikawa M, Yoshitomi T, Covey DF, Zorumski CF and Izumi Y: TSPO activation modulates the effects of high pressure in a rat ex vivo glaucoma model. Neuropharmacology. 111:142–159. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Papadopoulos V and Lecanu L: Translocator protein (18 kDa) TSPO: An emerging therapeutic target in neurotrauma. Exp Neurol. 219:53–57. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Girard C, Liu S, Adams D, Lacroix C, Sinéus M, Boucher C, Papadopoulos V, Rupprecht R, Schumacher M and Groyer G: Axonal regeneration and neuroinflammation: Roles for the translocator protein 18 kDa. J Neuroendocrinol. 24:71–81. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ravikumar B, Crawford D, Dellovade T, Savinainen A, Graham D, Liere P, Oudinet JP, Webb M and Hering H: Differential efficacy of the TSPO ligands etifoxine and XBD-173 in two rodent models of Multiple Sclerosis. Neuropharmacology. 108:229–237. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Choi HB, Khoo C, Ryu JK, van Breemen E, Kim SU and McLarnon JG: Inhibition of lipopolysaccharide-induced cyclooxygenase-2, tumor necrosis factor-alpha and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195. J Neurochem. 83:546–555. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Lebedeva IV, Su ZZ, Sarkar D, Kitada S, Dent P, Waxman S, Reed JC and Fisher PB: Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and inducing reactive oxygen species. Cancer Res. 63:8138–8144. 2003.PubMed/NCBI | |
|
Seneviratne MS, Faccenda D, De Biase V and Campanella M: PK11195 inhibits mitophagy targeting the F1Fo-ATPsynthase in Bcl-2 knock-down cells. Curr Mol Med. 12:476–482. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Bonora M, Giorgi C and Pinton P: Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 23:266–285. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Gonzalez-Polo RA, Carvalho G, Braun T, Decaudin D, Fabre C, Larochette N, Perfettini JL, Djavaheri-Mergny M, Youlyouz-Marfak I, Codogno P, et al: PK11195 potently sensitizes to apoptosis induction independently from the peripheral benzodiazepin receptor. Oncogene. 24:7503–7513. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Choi J, Ifuku M, Noda M and Guilarte TR: Translocator protein (18 kDa)/peripheral benzodiazepine receptor specific ligands induce microglia functions consistent with an activated state. Glia. 59:219–230. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Awad M and Gavish M: Binding of [3H]Ro 5-4864 and [3H]PK 11195 to cerebral cortex and peripheral tissues of various species: Species differences and heterogeneity in peripheral benzodiazepine binding sites. J Neurochem. 49:1407–1414. 1987. View Article : Google Scholar : PubMed/NCBI | |
|
Marangos PJ, Patel J, Boulenger JP and Clark-Rosenberg R: Characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864. Mol Pharmacol. 22:26–32. 1982.PubMed/NCBI | |
|
Kreisl WC, Kim MJ, Coughlin JM, Henter ID, Owen DR and Innis RB: PET imaging of neuroinflammation in neurological disorders. Lancet Neurol. 19:940–950. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Gut P, Baeza-Raja B, Andersson O, Hasenkamp L, Hsiao J, Hesselson D, Akassoglou K, Verdin E, Hirschey MD and Stainier DY: Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism. Nat Chem Biol. 9:97–104. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Da Pozzo E, Giacomelli C, Barresi E, Costa B, Taliani S, Passetti Fda S and Martini C: Targeting the 18-kDa translocator protein: recent perspectives for neuroprotection. Biochem Soc Trans. 43:559–565. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Gavioli EC, Duarte FS, Bressan E, Ferrara P, Farges RC and De Lima TC: Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test. Eur J Pharmacol. 471:21–26. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Kita A, Kohayakawa H, Kinoshita T, Ochi Y, Nakamichi K, Kurumiya S, Furukawa K and Oka M: Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br J Pharmacol. 142:1059–1072. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Baez E, Guio-Vega GP, Echeverria V, Sandoval-Rueda DA and Barreto GE: 4′-chlorodiazepam protects mitochondria in T98G astrocyte cell line from glucose deprivation. Neurotox Res. 32:163–171. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Nothdurfter C, Rammes G, Baghai TC, Schüle C, Schumacher M, Papadopoulos V and Rupprecht R: Translocator protein (18 kDa) as a target for novel anxiolytics with a favourable side-effect profile. J Neuroendocrinol. 24:82–92. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kita A, Kinoshita T, Kohayakawa H, Furukawa K and Akaike A: Lack of tolerance to anxiolysis and withdrawal symptoms in mice repeatedly treated with AC-5216, a selective TSPO ligand. Prog Neuropsychopharmacol Biol Psychiatry. 33:1040–1045. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Karlstetter M, Nothdurfter C, Aslanidis A, Moeller K, Horn F, Scholz R, Neumann H, Weber BH, Rupprecht R and Langmann T: Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. J Neuroinflammation. 11:32014. View Article : Google Scholar : PubMed/NCBI | |
|
Scholz R, Caramoy A, Bhuckory MB, Rashid K, Chen M, Xu H, Grimm C and Langmann T: Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration. J Neuroinflammation. 12:2012015. View Article : Google Scholar : PubMed/NCBI | |
|
Schlichter R, Rybalchenko V, Poisbeau P, Verleye M and Gillardin J: Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology. 39:1523–1535. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Choi YM and Kim KH: Etifoxine for pain patients with anxiety. Korean J Pain. 28:4–10. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Girard C, Liu S, Cadepond F, Adams D, Lacroix C, Verleye M, Gillardin JM, Baulieu EE, Schumacher M and Schweizer-Groyer G: Etifoxine improves peripheral nerve regeneration and functional recovery. Proc Natl Acad Sci USA. 105:20505–20510. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Olsen RW and Li GD: GABA(A) receptors as molecular targets of general anesthetics: Identification of binding sites provides clues to allosteric modulation. Can J Anaesth. 58:206–215. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Gunn BG, Brown AR, Lambert JJ and Belelli D: Neurosteroids and GABA(A) Receptor Interactions: A focus on stress. Front Neurosci. 5:1312011. View Article : Google Scholar : PubMed/NCBI | |
|
Biswas L, Ibrahim KS, Li X, Zhou X, Zeng Z, Craft J and Shu X: Effect of a TSPO ligand on retinal pigment epithelial cholesterol homeostasis in high-fat fed mice, implication for age-related macular degeneration. Exp Eye Res. 208:1086252021. View Article : Google Scholar : PubMed/NCBI | |
|
Ibrahim KS, Craft JA, Biswas L, Spencer J and Shu X: Etifoxine reverses weight gain and alters the colonic bacterial community in a mouse model of obesity. Biochem Pharmacol. 180:1141512020. View Article : Google Scholar : PubMed/NCBI | |
|
Costa B, Cavallini C, Da Pozzo E, Taliani S, Da Settimo F and Martini C: The anxiolytic etifoxine binds to TSPO Ro5-4864 binding site with long residence time showing a high neurosteroidogenic activity. ACS Chem Neurosci. 8:1448–1454. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kondo D, Saegusa H, Yabe R, Takasaki I, Kurihara T, Zong S and Tanabe T: Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice. J Pharmacol Sci. 110:55–63. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Tsukagoshi E, Kawaguchi M, Shinomiya T, Yoshikawa M, Kawano T, Okubo M and Sawaki K: Diazepam enhances production of diazepam-binding inhibitor (DBI), a negative saliva secretion regulator, localized in rat salivary gland. J Pharmacol Sci. 115:221–229. 2011. View Article : Google Scholar | |
|
Morin D, Musman J, Pons S, Berdeaux A and Ghaleh B: Mitochondrial translocator protein (TSPO): From physiology to cardioprotection. Biochem Pharmacol. 105:1–13. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Leducq N, Bono F, Sulpice T, Vin V, Janiak P, Fur GL, O'Connor SE and Herbert JM: Role of peripheral benzodiazepine receptors in mitochondrial, cellular, and cardiac damage induced by oxidative stress and ischemia-reperfusion. J Pharmacol Exp Ther. 306:828–837. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Santoro A, Mattace Raso G, Taliani S, Da Pozzo E, Simorini F, Costa B, Martini C, Laneri S, Sacchi A, Cosimelli B, et al: TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis. Eur J Pharm Sci. 88:124–131. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Klee K, Storti F, Barben M, Samardzija M, Langmann T, Dunaief J and Grimm C: Systemic knockout of Tspo in mice does not affect retinal morphology, function and susceptibility to degeneration. Exp Eye Res. 188:1078162019. View Article : Google Scholar : PubMed/NCBI | |
|
Storti F, Klee K, Todorova V, Steiner R, Othman A, van der Velde-Visser S, Samardzija M, Meneau I, Barben M, Karademir D, et al: Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration. Elife. 8:e451002019. View Article : Google Scholar : PubMed/NCBI | |
|
Santos AM, Calvente R, Tassi M, Carrasco MC, Martín-Oliva D, Marín-Teva JL, Navascués J and Cuadros MA: Embryonic and postnatal development of microglial cells in the mouse retina. J Comp Neurol. 506:224–239. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Lee MA, Sitko AA, Khalid S, Shirasu-Hiza M and Mason CA: Spatiotemporal distribution of glia in and around the developing mouse optic tract. J Comp Neurol. 527:508–521. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, et al: The classical complement cascade mediates CNS synapse elimination. Cell. 131:1164–1178. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Prinz M and Mildner A: Microglia in the CNS: Immigrants from another world. Glia. 59:177–187. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Banati RB, Middleton RJ, Chan R, Hatty CR, Kam WW, Quin C, Graeber MB, Parmar A, Zahra D, Callaghan P, et al: Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nat Commun. 5:54522014. View Article : Google Scholar : PubMed/NCBI | |
|
Barron AM, Ji B, Kito S, Suhara T and Higuchi M: Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male. Biochem J. 475:75–85. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Grassmann F, Fauser S and Weber BH: The genetics of age-related macular degeneration (AMD)-Novel targets for designing treatment options? Eur J Pharm Biopharm. 95:194–202. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Csader S, Korhonen S, Kaarniranta K and Schwab U: The effect of dietary supplementations on delaying the progression of age-related macular degeneration: A systematic review and meta-analysis. Nutrients. 14:42732022. View Article : Google Scholar : PubMed/NCBI | |
|
Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC, Wong WT and Chew EY: Age-related macular degeneration. Nat Rev Dis Primers. 7:312021. View Article : Google Scholar : PubMed/NCBI | |
|
Pikuleva IA and Curcio CA: Cholesterol in the retina: The best is yet to come. Prog Retin Eye Res. 41:64–89. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Curcio CA, Presley JB, Malek G, Medeiros NE, Avery DV and Kruth HS: Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res. 81:731–741. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Bhutto I and Lutty G: Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. Mol Aspects Med. 33:295–317. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Biesemeier A, Taubitz T, Julien S, Yoeruek E and Schraermeyer U: Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration. Neurobiol Aging. 35:2562–2573. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Fritsche LG, Igl W, Bailey JN, Grassmann F, Sengupta S, Bragg-Gresham JL, Burdon KP, Hebbring SJ, Wen C, Gorski M, et al: A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 48:134–143. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Toomey CB, Johnson LV and Bowes Rickman C: Complement factor H in AMD: Bridging genetic associations and pathobiology. Prog Retin Eye Res. 62:38–57. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Malek G, Johnson LV, Mace BE, Saloupis P, Schmechel DE, Rickman DW, Toth CA, Sullivan PM and Bowes Rickman C: Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration. Proc Natl Acad Sci USA. 102:11900–11905. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Toomey CB, Kelly U, Saban DR and Bowes Rickman C: Regulation of age-related macular degeneration-like pathology by complement factor H. Proc Natl Acad Sci USA. 112:E3040–E3049. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Langmann T: Microglia activation in retinal degeneration. J Leukoc Biol. 81:1345–1351. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Zeng H, Ding M, Chen XX and Lu Q: Microglial NADPH oxidase activation mediates rod cell death in the retinal degeneration in rd mice. Neuroscience. 275:54–61. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L, Zabel MK, Wang X, Ma W, Shah P, Fariss RN, Qian H, Parkhurst CN, Gan WB and Wong WT: Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO Mol Med. 7:1179–1197. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Farhan F, Almarhoun M, Wong A, Findlay AS, Bartholomew C, Williams MTS, Hurd TW and Shu X: Deletion of TSPO causes dysregulation of cholesterol metabolism in mouse retina. Cells. 10:30662021. View Article : Google Scholar : PubMed/NCBI | |
|
Luckoff A, Scholz R, Sennlaub F, Xu H and Langmann T: Comprehensive analysis of mouse retinal mononuclear phagocytes. Nat Protoc. 12:1136–1150. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Nagineni CN, Kommineni VK, William A, Detrick B and Hooks JJ: Regulation of VEGF expression in human retinal cells by cytokines: implications for the role of inflammation in age-related macular degeneration. J Cell Physiol. 227:116–126. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M and Melena J: Retinal ischemia: Mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res. 23:91–147. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Osborne NN, Ugarte M, Chao M, Chidlow G, Bae JH, Wood JP and Nash MS: Neuroprotection in relation to retinal ischemia and relevance to glaucoma. Surv Ophthalmol. 43 (Suppl 1):S102–S128. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Youngblood H, Robinson R, Sharma A and Sharma S: Proteomic biomarkers of retinal inflammation in diabetic retinopathy. Int J Mol Sci. 20:47552019. View Article : Google Scholar : PubMed/NCBI | |
|
Khayat M, Williams M and Lois N: Ischemic retinal vein occlusion: Characterizing the more severe spectrum of retinal vein occlusion. Surv Ophthalmol. 63:816–850. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Heyck M, Bonsack B, Zhang H, Sadanandan N, Cozene B, Kingsbury C, Lee JY and Borlongan CV: The brain and eye: Treating cerebral and retinal ischemia through mitochondrial transfer. Exp Biol Med (Maywood). 244:1485–1492. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Liu GJ, Middleton RJ, Kam WW, Chin DY, Hatty CR, Chan RH and Banati RB: Functional gains in energy and cell metabolism after TSPO gene insertion. Cell Cycle. 16:436–447. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ, Tanase D and Strother JM: Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes. 47:815–820. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Wagner L, Pannicke T, Rupprecht V, Frommherz I, Volz C, Illes P, Hirrlinger J, Jägle H, Egger V, Haydon PG, et al: Suppression of SNARE-dependent exocytosis in retinal glial cells and its effect on ischemia-induced neurodegeneration. Glia. 65:1059–1071. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dkhissi O, Chanut E, Wasowicz M, Savoldelli M, Nguyen-Legros J, Minvielle F and Versaux-Botteri C: Retinal TUNEL-positive cells and high glutamate levels in vitreous humor of mutant quail with a glaucoma-like disorder. Invest Ophthalmol Vis Sci. 40:990–995. 1999.PubMed/NCBI | |
|
Delyfer MN, Forster V, Neveux N, Picaud S, Leveillard T and Sahel JA: Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina. Mol Vis. 11:688–696. 2005.PubMed/NCBI | |
|
Vujosevic S, Aldington SJ, Silva P, Hernández C, Scanlon P, Peto T and Simó R: Screening for diabetic retinopathy: New perspectives and challenges. Lancet Diabetes Endocrinol. 8:337–347. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wang W and Lo ACY: Diabetic retinopathy: Pathophysiology and treatments. Int J Mol Sci. 19:18162018. View Article : Google Scholar : PubMed/NCBI | |
|
Fung TH, Patel B, Wilmot EG and Amoaku WM: Diabetic retinopathy for the non-ophthalmologist. Clin Med (Lond). 22:112–116. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Brownlee M: The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 54:1615–1625. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Naruse K, Nakamura J, Hamada Y, Nakayama M, Chaya S, Komori T, Kato K, Kasuya Y, Miwa K and Hotta N: Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. Exp Eye Res. 71:309–315. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Romeo G, Liu WH, Asnaghi V, Kern TS and Lorenzi M: Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes. 51:2241–2248. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Abcouwer SF: Muller cell-microglia cross talk drives neuroinflammation in diabetic retinopathy. Diabetes. 66:261–263. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sorrentino FS, Allkabes M, Salsini G, Bonifazzi C and Perri P: The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy. Life Sci. 162:54–59. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Podesta F, Romeo G, Liu WH, Krajewski S, Reed JC, Gerhardinger C and Lorenzi M: Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. Am J Pathol. 156:1025–1032. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Tien T, Zhang J, Muto T, Kim D, Sarthy VP and Roy S: High glucose induces mitochondrial dysfunction in retinal muller cells: Implications for diabetic retinopathy. Invest Ophthalmol Vis Sci. 58:2915–2921. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sasaki M, Ozawa Y, Kurihara T, Kubota S, Yuki K, Noda K, Kobayashi S, Ishida S and Tsubota K: Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes. Diabetologia. 53:971–979. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li J and Papadopoulos V: Translocator protein (18 kDa) as a pharmacological target in adipocytes to regulate glucose homeostasis. Biochem Pharmacol. 97:99–110. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Musman J, Paradis S, Panel M, Pons S, Barau C, Caccia C, Leoni V, Ghaleh B and Morin D: A TSPO ligand prevents mitochondrial sterol accumulation and dysfunction during myocardial ischemia-reperfusion in hypercholesterolemic rats. Biochem Pharmacol. 142:87–95. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ciudin A, Simo-Servat O, Hernandez C, Arcos G, Diego S, Sanabria Á, Sotolongo Ó, Hernández I, Boada M and Simó R: Retinal Microperimetry: A new tool for identifying patients with type 2 diabetes at risk for developing Alzheimer disease. Diabetes. 66:3098–3104. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kinuthia UM, Wolf A and Langmann T: Microglia and inflammatory responses in diabetic retinopathy. Front Immunol. 11:5640772020. View Article : Google Scholar : PubMed/NCBI | |
|
Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, Das A, Jonas JB, Keeffe J, Kempen JH, et al: Global causes of blindness and distance vision impairment 1990–2020: A systematic review and meta-analysis. Lancet Glob Health. 5:e1221–e1234. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Tham YC, Li X, Wong TY, Quigley HA, Aung T and Cheng CY: Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 121:2081–2090. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Zukerman R, Harris A, Oddone F, Siesky B, Verticchio Vercellin A and Ciulla TA: Glaucoma heritability: Molecular mechanisms of disease. Genes (Basel). 12:11352021. View Article : Google Scholar : PubMed/NCBI | |
|
Quigley HA: Glaucoma. Lancet. 377:1367–1377. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Ishikawa M, Yoshitomi T, Zorumski CF and Izumi Y: Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model. Invest Ophthalmol Vis Sci. 55:8531–8541. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Belelli D and Lambert JJ: Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 6:565–575. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Weir CJ, Ling AT, Belelli D, Wildsmith JA, Peters JA and Lambert JJ: The interaction of anaesthetic steroids with recombinant glycine and GABAA receptors. Br J Anaesth. 92:704–711. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Midzak A, Akula N, Lecanu L and Papadopoulos V: Novel androstenetriol interacts with the mitochondrial translocator protein and controls steroidogenesis. J Biol Chem. 286:9875–9887. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Izumi Y, Benz AM, Kurby CO, Labruyere J, Zorumski CF, Price MT and Olney JW: An ex vivo rat retinal preparation for excitotoxicity studies. J Neurosci Methods. 60:219–225. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Izumi Y, Kirby CO, Benz AM, Olney JW and Zorumski CF: Muller cell swelling, glutamate uptake, and excitotoxic neurodegeneration in the isolated rat retina. Glia. 25:379–389. 1999. View Article : Google Scholar : PubMed/NCBI |
