Özet
ABSTRACT
Aysun G. Evaluation of Serum Sirtuin and Adiponectin Levels in patients with Primary Open-Angle Glaucoma and Exfoliative Glaucoma, Ankara, 2018.
The aim of this study is to compare the serum sirtuin 1 (SIRT1) and adiponectin levels in patients with primary open-angle glaucoma (POAG) and exfoliative glaucoma (EG) with healthy control subjects over 50 years of age. Blood samples were collected from 40 patients with POAG, 38 patients with EG and 40 individuals over 50 years of age with no systemic or ocular disease. Serum SIRT1 and adiponectin was estimated by Enzyme Linked Immunosorbent Assay (ELISA). In patients with POAG (0.731 ng / ml), a significant (p = 0.004) decrease in SIRT1 concentration was observed compared to controls (1.423 ng / ml). Statistically significant difference was not found in patients with EG (1.155 ng / ml) compared to controls and patients with POAG (p=0,345, p=0,325). There was no statistically significant difference in serum adiponectin levels between the 3 groups (p=0.590). There was no statistically significant difference found to the distribution of SIRT1 levels by sex (p=0.343). Serum adiponectin levels were significantly (p=0.002) higher in women. In conclusion; in this study, serum SIRT1 level was found to be lower in patients with POAG than control subjects. There was no statistically significant difference in adiponectin levels between the 3 groups. Our results suggest that SIRT1 may play a protective role in POAG.
Key words: Primary open angle glaucoma, exfoliative glaucoma, sirtuin, adiponectin, neurodegeneration
Künye
KAYNAKLAR
1. Allingham RR, Damji KF, Freedman SF, Moroi SE, Rhee DJ, Shields MB. Shields textbook of glaucoma: Lippincott Williams & Wilkins; 2012; 7(2): 1-425.
2. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-90.
3. Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S. Glaucoma. Lancet. 2017;390(10108):2183-93.
4. Evangelho K, Mogilevskaya M, Losada-Barragan M, Vargas-Sanchez JK. Pathophysiology of primary open-angle glaucoma from a neuroinflammatory and neurotoxicity perspective: a review of the literature. Int Ophthalmol. 2017.
5. Xu C, Li J, Li Z, Mao X. Migraine as a risk factor for primary open angle glaucoma: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(28):e11377.
6. Shi Y, Liu P, Guan J, Lu Y, Su K. Association between glaucoma and obstructive sleep apnea syndrome: a meta-analysis and systematic review. PLoS One. 2015;10(2):e0115625.
7. Zhao D, Cho J, Kim MH, Friedman DS, Guallar E. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology. 2015;122(1):72-8.
8. Zhao D, Cho J, Kim MH, Guallar E. The association of blood pressure and primary open-angle glaucoma: a meta-analysis. Am J Ophthalmol. 2014;158(3):615-27 e9.
9. Ritch R. Exfoliation syndrome-the most common identifiable cause of open-angle glaucoma. J Glaucoma. 1994;3(2):176-7.
10. Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S. The role of SIRT1 in ocular aging. Exp Eye Res. 2013;116:17-26.
11. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270(45):26746-9.
12. Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest. 2001;108(12):1875-81.
13. European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 2: Classification and Terminology Supported by the EGS Foundation: Part 1: Foreword; Introduction; Glossary; Chapter 2 Classification and Terminology. Br J Ophthalmol. 2017;101(5):73-127.
14. Quigley HA, Broman AT. The Number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-7.
15. Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol. 2016;100(1):86-93.
16. Anderson DR, Drance SM, Schulzer M, Collaborative Normal-Tension Glaucoma Study G. Factors that predict the benefit of lowering intraocular pressure in normal tension glaucoma. Am J Ophthalmol. 2003;136(5):820-9.
17. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013;120(8):1533-40.
18. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship between glaucoma and myopia: the Blue Mountains Eye Study. Ophthalmology. 1999;106(10):2010-5.
19. Leske MC, Wu SY, Nemesure B, Hennis A. Incident open-angle glaucoma and blood pressure. Arch Ophthalmol. 2002;120(7):954-9.
20. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol. 1981;99(4):635-49.
21. Chung HS, Harris A, Evans DW, Kagemann L, Garzozi HJ, Martin B. Vascular aspects in the pathophysiology of glaucomatous optic neuropathy. Surv Ophthalmol. 1999;43 Suppl 1:S43-50.
22. Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005;24(1):39-73.
23. Almasieh M, Wilson AM, Morquette B, Cueva Vargas JL, Di Polo A. The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res. 2012;31(2):152-81.
24. Salinas-Navarro M, Alarcon-Martinez L, Valiente-Soriano FJ, Jimenez-Lopez M, Mayor-Torroglosa S, Aviles-Trigueros M, et al. Ocular hypertension impairs optic nerve axonal transport leading to progressive retinal ganglion cell degeneration. Exp Eye Res. 2010;90(1):168-83.
25. Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ. Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci. 2000;41(3):764-74.
26. Yu DY, Cringle SJ, Balaratnasingam C, Morgan WH, Yu PK, Su EN. Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability. Prog Retin Eye Res. 2013;36:217-46.
27. Ju WK, Kim KY, Lindsey JD, Angert M, Duong-Polk KX, Scott RT, et al. Intraocular pressure elevation induces mitochondrial fission and triggers OPA1 release in glaucomatous optic nerve. Invest Ophthalmol Vis Sci. 2008;49(11):4903-11.
28. Balaratnasingam C, Kang MH, Yu P, Chan G, Morgan WH, Cringle SJ, et al. Comparative quantitative study of astrocytes and capillary distribution in optic nerve laminar regions. Exp Eye Res. 2014;121:11-22.
29. Naskar R, Vorwerk CK, Dreyer EB. Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci. 2000;41(7):1940-4.
30. Hare WA, WoldeMussie E, Lai RK, Ton H, Ruiz G, Chun T, et al. Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, I: Functional measures. Invest Ophthalmol Vis Sci. 2004;45(8):2625-39.
31. Hare WA, WoldeMussie E, Weinreb RN, Ton H, Ruiz G, Wijono M, et al. Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures. Invest Ophthalmol Vis Sci. 2004;45(8):2640-51.
32. WoldeMussie E, Yoles E, Schwartz M, Ruiz G, Wheeler LA. Neuroprotective effect of memantine in different retinal injury models in rats. J Glaucoma. 2002;11(6):474-80.
33. Banerjee D, Banerjee A, Mookherjee S, Vishal M, Mukhopadhyay A, Sen A, et al. Mitochondrial genome analysis of primary open angle glaucoma patients. PLoS One. 2013;8(8):e70760.
34. Crish SD, Sappington RM, Inman DM, Horner PJ, Calkins DJ. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc Natl Acad Sci U S A. 2010;107(11):5196-201.
35. Cordeiro MF, Migdal C, Bloom P, Fitzke FW, Moss SE. Imaging apoptosis in the eye. Eye (Lond). 2011;25(5):545-53.
36. Liu M, Wu W, Li H, Li S, Huang LT, Yang YQ, et al. Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice. J Spinal Cord Med. 2015;38(6):745-53.
37. Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci. 1995;36(5):774-86.
38. Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280-93.
39. Deng S, Wang M, Yan Z, Tian Z, Chen H, Yang X, et al. Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model. PLoS One. 2013;8(10):e77100.
40. Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A, et al. Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci U S A. 2007;104(33):13444-9.
41. Hernandez MR. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 2000;19(3):297-321.
42. Lye-Barthel M, Sun D, Jakobs TC. Morphology of astrocytes in a glaucomatous optic nerve. Invest Ophthalmol Vis Sci. 2013;54(2):909-17.
43. Fukuchi T, Sawaguchi S, Hara H, Shirakashi M, Iwata K. Extracellular matrix changes of the optic nerve lamina cribrosa in monkey eyes with experimentally chronic glaucoma. Graefes Arch Clin Exp Ophthalmol. 1992;230(5):421-7.
44. Zeng HL, Shi JM. The role of microglia in the progression of glaucomatous neurodegeneration- a review. Int J Ophthalmol. 2018;11(1):143-9.
45. Wax MB. The case for autoimmunity in glaucoma. Exp Eye Res. 2011;93(2):187-90.
46. Kasim B, Irkec M, Alikasifoglu M, Orhan M, Mocan MC, Aktas D. Association of LOXL1 gene polymorphisms with exfoliation syndrome/glaucoma and primary open angle glaucoma in a Turkish population. Mol Vis. 2013;19:114-20.
47. Ritch R. Systemic Associations of Exfoliation Syndrome. Asia Pac J Ophthalmol (Phila). 2016;5(1):45-50.
48. Ritch R. Ocular Findings in Exfoliation Syndrome. Journal of glaucoma. 2018;27 Suppl 1:S67-s71.
49. Sekeroglu MA, Bozkurt B, Irkec M, Ustunel S, Orhan M, Saracbasi O. Systemic associations and prevalence of exfoliation syndrome in patients scheduled for cataract surgery. Eur J Ophthalmol. 2008;18(4):551-5.
50. Mitchell P, Wang JJ, Smith W. Association of pseudoexfoliation syndrome with increased vascular risk. Am J Ophthalmol. 1997;124(5):685-7.
51. Irkec M. Exfoliation and carotid stiffness. Br J Ophthalmol. 2006;90(5):529-30.
52. Schumacher S, Schlotzer-Schrehardt U, Martus P, Lang W, Naumann GO. Pseudoexfoliation syndrome and aneurysms of the abdominal aorta. Lancet (London, England). 2001;357(9253):359-60.
53. Gonen KA, Gonen T, Gumus B. Reply: Pseudoexfoliation syndrome and cardiovascular disease: studies must control for all cardiovascular risk factors. Eye (Lond). 2013;27(11):1329.
54. Tanito M, Kaidzu S, Takai Y, Ohira A. Status of systemic oxidative stresses in patients with primary open-angle glaucoma and pseudoexfoliation syndrome. PLoS One. 2012;7(11):e49680.
55. Linner E, Popovic V, Gottfries CG, Jonsson M, Sjogren M, Wallin A. The exfoliation syndrome in cognitive impairment of cerebrovascular or Alzheimer's type. Acta ophthalmologica Scandinavica. 2001;79(3):283-5.
56. Ekstrom C, Kilander L. Pseudoexfoliation and Alzheimer's disease: a population-based 30-year follow-up study. Acta Ophthalmol. 2014;92(4):355-8.
57. Paliobei VP, Psillas GK, Mikropoulos DG, Haidich AB, Constantinidis J, Konstas AG. Hearing Evaluation in Patients with Exfoliative and Primary Open-Angle Glaucoma. Otolaryngol Head Neck Surg. 2011;145(1):125-30.
58. Singham NV, Zahari M, Peyman M, Prepageran N, Subrayan V. Association between Ocular Pseudoexfoliation and Sensorineural Hearing Loss. J Ophthalmol. 2014;2014:825936.
59. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene. 2005;363:15-23.
60. Gray SG, Ekstrom TJ. The human histone deacetylase family. Exp Cell Res. 2001;262(2):75-83.
61. Feldman JL, Dittenhafer-Reed KE, Denu JM. Sirtuin catalysis and regulation. J Biol Chem. 2012;287(51):42419-27.
62. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000;273(2):793-8.
63. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. 2006;4(2):e31.
64. Banks AS, Kon N, Knight C, Matsumoto M, Gutierrez-Juarez R, Rossetti L, et al. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 2008;8(4):333-41.
65. Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007;28(1):91-106.
66. Trotta PA, Moura EG, Franco JG, Lima NS, de Oliveira E, Cordeiro A, et al. Blocking leptin action one week after weaning reverts most of the programming caused by neonatal hyperleptinemia in the adult rat. Horm Metab Res. 2011;43(3):171-7.
67. Picard F, Guarente L. Molecular links between aging and adipose tissue. Int J Obes (Lond). 2005;29 Suppl 1:S36-9.
68. Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007;6(4):307-19.
69. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004;429(6993):771-6.
70. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W. Negative regulation of the deacetylase SIRT1 by DBC1. Nature. 2008;451(7178):587-90.
71. Kim JE, Chen J, Lou Z. DBC1 is a negative regulator of SIRT1. Nature. 2008;451(7178):583-6.
72. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008;14(4):312-23.
73. Yuan J, Minter-Dykhouse K, Lou Z. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation. J Cell Biol. 2009;185(2):203-11.
74. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253-95.
75. Li K, Casta A, Wang R, Lozada E, Fan W, Kane S, et al. Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation. J Biol Chem. 2008;283(12):7590-8.
76. Sinclair DA, Mills K, Guarente L. Molecular mechanisms of yeast aging. Trends Biochem Sci. 1998;23(4):131-4.
77. Palladino F, Laroche T, Gilson E, Axelrod A, Pillus L, Gasser SM. SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres. Cell. 1993;75(3):543-55.
78. Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell. 2005;120(4):473-82.
79. Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci U S A. 2003;100(19):10794-9.
80. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 2007;6(6):759-67.
81. Hsu YJ, Hsu SC, Hsu CP, Chen YH, Chang YL, Sadoshima J, et al. Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model. Int J Cardiol. 2017;228:543-52.
82. Prola A, Pires Da Silva J, Guilbert A, Lecru L, Piquereau J, Ribeiro M, et al. SIRT1 protects the heart from ER stress-induced cell death through eIF2alpha deacetylation. Cell Death Differ. 2017;24(2):343-56.
83. Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, et al. Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004;116(4):551-63.
84. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):2011-5.
85. Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004;305(5686):1010-3.
86. Chen D, Steele AD, Hutter G, Bruno J, Govindarajan A, Easlon E, et al. The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration. Exp Gerontol. 2008;43(12):1086-93.
87. Cornelius C, Trovato Salinaro A, Scuto M, Fronte V, Cambria MT, Pennisi M, et al. Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes. Immun Ageing. 2013;10(1):41.
88. Herskovits AZ, Guarente L. Sirtuin deacetylases in neurodegenerative diseases of aging. Cell Res. 2013;23(6):746-58.
89. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. J Neuroinflammation. 2017;14(1):1.
90. Bonda DJ, Lee HG, Camins A, Pallas M, Casadesus G, Smith MA, et al. The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations. Lancet Neurol. 2011;10(3):275-9.
91. Donmez G, Arun A, Chung CY, McLean PJ, Lindquist S, Guarente L. SIRT1 protects against alpha-synuclein aggregation by activating molecular chaperones. J Neurosci. 2012;32(1):124-32.
92. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med. 2011;18(1):153-8.
93. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177(8):861-70.
94. Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, et al. SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol. 2009;29(5):1363-74.
95. Schug TT, Xu Q, Gao H, Peres-da-Silva A, Draper DW, Fessler MB, et al. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol. 2010;30(19):4712-21.
96. Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A. 2008;105(28):9793-8.
97. Zhao S, Li T, Li J, Lu Q, Han C, Wang N, et al. miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway. Diabetologia. 2016;59(3):644-54.
98. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, et al. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2007;104(37):14855-60.
99. Ota H, Akishita M, Eto M, Iijima K, Kaneki M, Ouchi Y. Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol. 2007;43(5):571-9.
100. McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, et al. The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol. 2003;23(1):38-54.
101. Kamel C, Abrol M, Jardine K, He X, McBurney MW. SirT1 fails to affect p53-mediated biological functions. Aging Cell. 2006;5(1):81-8.
102. Jaliffa C, Ameqrane I, Dansault A, Leemput J, Vieira V, Lacassagne E, et al. Sirt1 involvement in rd10 mouse retinal degeneration. Invest Ophthalmol Vis Sci. 2009;50(8):3562-72.
103. Maloney SC, Antecka E, Odashiro AN, Fernandes BF, Doyle M, Lim LA, et al. Expression of SIRT1 and DBC1 in Developing and Adult Retinas. Stem Cells Int. 2012;2012:908183.
104. Zheng T, Lu Y. SIRT1 Protects Human Lens Epithelial Cells Against Oxidative Stress by Inhibiting p53-Dependent Apoptosis. Curr Eye Res. 2016;41(8):1068-75.
105. Zheng Y, Liu Y, Ge J, Wang X, Liu L, Bu Z, et al. Resveratrol protects human lens epithelial cells against H2O2-induced oxidative stress by increasing catalase, SOD-1, and HO-1 expression. Mol Vis. 2010;16:1467-74.
106. Lin TJ, Peng CH, Chiou SH, Liu JH, Lin Chung W, Tsai CY, et al. Severity of lens opacity, age, and correlation of the level of silent information regulator T1 expression in age-related cataract. J Cataract Refract Surg. 2011;37(7):1270-4.
107. Zheng T, Lu Y. Changes in SIRT1 expression and its downstream pathways in age-related cataract in humans. Curr Eye Res. 2011;36(5):449-55.
108. Chen Z, Zhai Y, Zhang W, Teng Y, Yao K. Single Nucleotide Polymorphisms of the Sirtuin 1 (SIRT1) Gene are Associated With age-Related Macular Degeneration in Chinese Han Individuals: A Case-Control Pilot Study. Medicine (Baltimore). 2015;94(49):e2238.
109. Maloney SC, Antecka E, Granner T, Fernandes B, Lim LA, Orellana ME, et al. Expression of SIRT1 in choroidal neovascular membranes. Retina. 2013;33(4):862-6.
110. Balaiya S, Khetpal V, Chalam KV. Hypoxia initiates sirtuin1-mediated vascular endothelial growth factor activation in choroidal endothelial cells through hypoxia inducible factor-2alpha. Mol Vis. 2012;18:114-20.
111. Zhuge CC, Xu JY, Zhang J, Li W, Li P, Li Z, et al. Fullerenol protects retinal pigment epithelial cells from oxidative stress-induced premature senescence via activating SIRT1. Invest Ophthalmol Vis Sci. 2014;55(7):4628-38.
112. Cao L, Liu C, Wang F, Wang H. SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-kappaB pathway. Braz J Med Biol Res. 2013;46(8):659-69.
113. Cheung CM, Vania M, Ang M, Chee SP, Li J. Comparison of aqueous humor cytokine and chemokine levels in diabetic patients with and without retinopathy. Mol Vis. 2012;18:830-7.
114. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70.
115. Chen M, Curtis TM, Stitt AW. Advanced glycation end products and diabetic retinopathy. Curr Med Chem. 2013;20(26):3234-40.
116. de Moraes G, Layton CJ. Therapeutic targeting of diabetic retinal neuropathy as a strategy in preventing diabetic retinopathy. Clin Exp Ophthalmol. 2016;44(9):838-52.
117. Kowluru RA, Koppolu P, Chakrabarti S, Chen S. Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants. Free Radic Res. 2003;37(11):1169-80.
118. Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H. Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc Natl Acad Sci U S A. 2012;109(39):15888-93.
119. Xu H, Cai M, Zhang X. Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats. Graefes Arch Clin Exp Ophthalmol. 2015;253(9):1485-92.
120. Liu S, Lin YU, Liu X. Protective effects of SIRT1 in patients with proliferative diabetic retinopathy via the inhibition of IL-17 expression. Exp Ther Med. 2016;11(1):257-62.
121. Mortuza R, Chen S, Feng B, Sen S, Chakrabarti S. High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway. PLoS One. 2013;8(1):e54514.
122. Kowluru RA, Santos JM, Zhong Q. Sirt1, a negative regulator of matrix metalloproteinase-9 in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014;55(9):5653-60.
123. Quinn TA, Dutt M, Shindler KS. Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis. Front Neurol. 2011;2:50.
124. Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A. SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci. 2007;48(8):3602-9.
125. Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M, et al. Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol. 2012;3:84.
126. Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2010;30(4):328-39.
127. Khan RS, Fonseca-Kelly Z, Callinan C, Zuo L, Sachdeva MM, Shindler KS. SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells. Front Cell Neurosci. 2012;6:63.
128. Kim SH, Park JH, Kim YJ, Park KH. The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection. Mol Vis. 2013;19:1667-76.
129. Zuo L, Khan RS, Lee V, Dine K, Wu W, Shindler KS. SIRT1 promotes RGC survival and delays loss of function following optic nerve crush. Invest Ophthalmol Vis Sci. 2013;54(7):5097-102.
130. Balaiya S, Ferguson LR, Chalam KV. Evaluation of sirtuin role in neuroprotection of retinal ganglion cells in hypoxia. Invest Ophthalmol Vis Sci. 2012;53(7):4315-22.
131. Kim SJ, Sung MS, Heo H, Lee JH, Park SW. Mangiferin Protects Retinal Ganglion Cells in Ischemic Mouse Retina via SIRT1. Curr Eye Res. 2016;41(6):844-55.
132. Yang X, Cai J, Powell DW, Paladugu H, Kuehn MH, Tezel G. Up-regulation of sirtuins in the glaucomatous human retina. Investigative Ophthalmology & Visual Science. 2014;55(13):2398-.
133. Yi X, Feng G, Zhou Y, Jiang X. Sirtuin 1 activation and cardioprotective role: Thy eternal summer shall not fade. Int J Cardiol. 2017;247:29.
134. Tang BL. Sirtuins as modifiers of Parkinson's disease pathology. J Neurosci Res. 2017;95(4):930-42.
135. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. Embo j. 2007;26(13):3169-79.
136. Covington JD, Bajpeyi S. The sirtuins: Markers of metabolic health. Mol Nutr Food Res. 2016;60(1):79-91.
137. O'Callaghan C, Vassilopoulos A. Sirtuins at the crossroads of stemness, aging, and cancer. Aging Cell. 2017;16(6):1208-18.
138. Rizzi L, Roriz-Cruz M. Sirtuin 1 and Alzheimer's disease: An up-to-date review. Neuropeptides. 2018;71:54-60.
139. Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18(6).
140. Bełtowski J, Jamroz-Wiśniewska A, Widomska S. Adiponectin and its role in cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets. 2008;8(1):7-46.
141. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab. 2001;86(8):3815-9.
142. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784-92.
143. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332-9.
144. Shrestha A, Park PH. Globular adiponectin attenuates LPS-induced reactive oxygen species production in HepG2 cells via FoxO3A and HO-1 signaling. Life Sci. 2016;148:71-9.
145. Park PH, Huang H, McMullen MR, Mandal P, Sun L, Nagy LE. Suppression of lipopolysaccharide-stimulated tumor necrosis factor-alpha production by adiponectin is mediated by transcriptional and post-transcriptional mechanisms. J Biol Chem. 2008;283(40):26850-8.
146. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004;109(17):2046-9.
147. Lyzogubov VV, Tytarenko RG, Bora NS, Bora PS. Inhibitory role of adiponectin peptide I on rat choroidal neovascularization. Biochim Biophys Acta. 2012;1823(8):1264-72.
148. Cao G, Chen Y, Zhang J, Liu Y, Zhang M, Zhang K, et al. Effects of adiponectin polymorphisms on the risk of advanced age-related macular degeneration. Biomarkers. 2015;20(4):266-70.
149. Kaarniranta K, Paananen J, Nevalainen T, Sorri I, Seitsonen S, Immonen I, et al. Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population. Neurosci Lett. 2012;513(2):233-7.
150. Hadjadj S, Aubert R, Fumeron F, Pean F, Tichet J, Roussel R, et al. Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects. Diabetologia. 2005;48(6):1088-92.
151. Jung CH, Kim BY, Mok JO, Kang SK, Kim CH. Association between serum adipocytokine levels and microangiopathies in patients with type 2 diabetes mellitus. J Diabetes Investig. 2014;5(3):333-9.
152. Letra L, Rodrigues T, Matafome P, Santana I, Seica R. Adiponectin and sporadic Alzheimer's disease: Clinical and molecular links. Front Neuroendocrinol. 2017.
153. Chan KH, Lam KS, Cheng OY, Kwan JS, Ho PW, Cheng KK, et al. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity. PLoS One. 2012;7(12):e52354.
154. Song J, Kang SM, Kim E, Kim CH, Song HT, Lee JE. Adiponectin receptor-mediated signaling ameliorates cerebral cell damage and regulates the neurogenesis of neural stem cells at high glucose concentrations: an in vivo and in vitro study. Cell Death Dis. 2015;6:e1844.
155. Qiu G, Wan R, Hu J, Mattson MP, Spangler E, Liu S, et al. Adiponectin protects rat hippocampal neurons against excitotoxicity. Age (Dordr). 2011;33(2):155-65.
156. Ali T, Yoon GH, Shah SA, Lee HY, Kim MO. Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus. Sci Rep. 2015;5:11708.
157. Ng RC, Cheng OY, Jian M, Kwan JS, Ho PW, Cheng KK, et al. Chronic adiponectin deficiency leads to Alzheimer's disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice. Mol Neurodegener. 2016;11(1):71.
158. Khemka VK, Bagchi D, Bandyopadhyay K, Bir A, Chattopadhyay M, Biswas A, et al. Altered serum levels of adipokines and insulin in probable Alzheimer's disease. J Alzheimers Dis. 2014;41(2):525-33.
159. Ma J, Zhang W, Wang HF, Wang ZX, Jiang T, Tan MS, et al. Peripheral Blood Adipokines and Insulin Levels in Patients with Alzheimer's Disease: A Replication Study and Meta-Analysis. Curr Alzheimer Res. 2016;13(3):223-33.
160. Teixeira AL, Diniz BS, Campos AC, Miranda AS, Rocha NP, Talib LL, et al. Decreased levels of circulating adiponectin in mild cognitive impairment and Alzheimer's disease. Neuromolecular Med. 2013;15(1):115-21.
161. Une K, Takei YA, Tomita N, Asamura T, Ohrui T, Furukawa K, et al. Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer's disease. Eur J Neurol. 2011;18(7):1006-9.
162. Ng RC, Chan KH. Potential Neuroprotective Effects of Adiponectin in Alzheimer's Disease. Int J Mol Sci. 2017;18(3).
163. Trovato Salinaro A, Cornelius C, Koverech G, Koverech A, Scuto M, Lodato F, et al. Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer's disease. Front Pharmacol. 2014;5:129.
164. Soto I, Howell GR. The complex role of neuroinflammation in glaucoma. Cold Spring Harb Perspect Med. 2014;4(8).
165. Criscuolo C, Fabiani C, Cerri E, Domenici L. Synaptic Dysfunction in Alzheimer's Disease and Glaucoma: From Common Degenerative Mechanisms Toward Neuroprotection. Front Cell Neurosci. 2017;11:53.
166. Cumurcu T, Dorak F, Cumurcu BE, Erbay LG, Ozsoy E. Is there any relation between pseudoexfoliation syndrome and Alzheimer's type dementia? Semin Ophthalmol. 2013;28(4):224-9.
167. Lu G, Li J, Zhang H, Zhao X, Yan LJ, Yang X. Role and Possible Mechanisms of Sirt1 in Depression. Oxid Med Cell Longev. 2018;2018:8596903.
168. Rizzi L, Roriz-Cruz M. Sirtuin 1 and Alzheimer's disease: An up-to-date review. Neuropeptides. 2018.
169. Jesko H, Wencel P, Strosznajder RP, Strosznajder JB. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochem Res. 2017;42(3):876-90.
170. Wencel PL, Lukiw WJ, Strosznajder JB, Strosznajder RP. Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity. Mol Neurobiol. 2018;55(6):4612-23.
171. Wang J, Fivecoat H, Ho L, Pan Y, Ling E, Pasinetti GM. The role of Sirt1: at the crossroad between promotion of longevity and protection against Alzheimer's disease neuropathology. Biochim Biophys Acta. 2010;1804(8):1690-4.
172. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell. 2010;142(2):320-32.
173. Kumar R, Chaterjee P, Sharma PK, Singh AK, Gupta A, Gill K, et al. Sirtuin1: a promising serum protein marker for early detection of Alzheimer's disease. PLoS One. 2013;8(4):e61560.
174. Kondo A, Goto M, Mimura T, Matsubara M. Silent information regulator T1 in aqueous humor of patients with cataract. Clin Ophthalmol. 2016;10:307-12.
175. Li P, Zhang L, Zhou C, Lin N, Liu A. Sirt 1 activator inhibits the AGE-induced apoptosis and p53 acetylation in human vascular endothelial cells. J Toxicol Sci. 2015;40(5):615-24.
176. Bigalke B, Schreitmuller B, Sopova K, Paul A, Stransky E, Gawaz M, et al. Adipocytokines and CD34 progenitor cells in Alzheimer's disease. PLoS One. 2011;6(5):e20286.
177. Kuo JZ, Guo X, Klein R, Klein BE, Genter P, Roll K, et al. Adiponectin, Insulin Sensitivity and Diabetic Retinopathy in Latinos With Type 2 Diabetes. J Clin Endocrinol Metab. 2015;100(9):3348-55.
178. Mao D, Peng H, Li Q, Wang J, Li P, Hu K, et al. Aqueous humor and plasma adiponectin levels in proliferative diabetic retinopathy patients. Curr Eye Res. 2012;37(9):803-8.
179. Zietz B, Buechler C, Kobuch K, Neumeier M, Scholmerich J, Schaffler A. Serum levels of adiponectin are associated with diabetic retinopathy and with adiponectin gene mutations in Caucasian patients with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes. 2008;116(9):532-6.
180. Kato K, Osawa H, Ochi M, Kusunoki Y, Ebisui O, Ohno K, et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy. Clin Endocrinol (Oxf). 2008;68(3):442-9.
