Retinal Inflammaging: Pathogenesis and Prevention
Abstract
Macula lutea, the yellow sot or fovea centralis in eye serves the distinctive central vision in perceiving visual cues and contributing to task performance. Impaired visual acuity in later years in life, compromises safety, productivity and life quality. Carotenoid pigment content declines with cumulation of light induced damage through aging process in retina. The progression of resultant macular degeneration is aggravated by oxidative stress, inflammation, raised blood sugar and vasculopathy associating aging. Senescent dry degeneration involves drusen (a compound of glycolipid and glycol-conjugate core) deposition that impairs metabolic connectivity of upper layers of retina with choroid. Degeneration of retinal pigment epithelium (RPE) and photoreceptors thus, results. The late more severe form of age related macular degeneration (AMD), involves factors inducing choroidal neo-vascularization. Leaky neo-capillaries speed degenerative process of retina. Most age related pathologies are initiated by metabolic disruptions and AMD shares features of systemic atherosclerosis. An aberrant tissue response to free radical stress, vasculopathy and local ischaemic underlies AMD pathogenesis.
There is no specific treatment modality and prudent strategy in prophylaxis only. Early diagnosis and proper control of environmental and lifestyle factors are strived by newer biomedical understanding, which is briefly reviewed.References
1. Krishnan T Ravindran RD Murthy GVS Vashist P Fitzpatrick KE Thulasoraj RD et al Prevalence of early and late age related macular degeneration in India:the INDEYE study Invest Ophthalmol Vis Sci 2010 51 :701-707
2. Voutilinen-Kaunisto RM Terasvirta ME Usirupa MIJ Age related macular degeneration in newly diagnosed type 2 diabetes patients and control subjects Diabetes Care 2000 23 1672-1678
3. Sander B, Larsen M Meldow B Diabetic macular oedema:passive and active transport of fluorescine through the blood retina barrier. Invest Ophthalmol Vis Sci 2001, 42:433-438.
4. Bhutto I, Lutty G Understanding age related macular degeneration(AMD):relationships between the photoreceptor/retinal pigment epithelium/Bruchs membrane/choriocapillaris complex Molecular Aspects of Medicine 2012 33:295-317
5. Machalinska A Kawa MP Marlicz WS Complement system activation and endothelial dysfunction in patients with age related macular degeneration:possible relation between AMD and atherosclerosis Acta Ophthalmol 2012 90 695-703
6. Machalinska A Dziedziejko V Mazolevska-Piotrovska K Elevated plasma levels of C3a complement compound in the exudative form of AMD Ophthalmic Res 2009 42 54-59
7. Reynolds R Hartnett ME Atkinson JP Plasma complement components and activation fragment associations with AMD genotypes and phenotypes Invest Ophthalmol Vis Sci 2009 50 5818-5827
8. Seddom JM Rifai M Association with C reactive protein and age related macular degeneration JAMA 2004 281 704-710
9. Verma S Anderson TJ Fundamentals of endothelial function for the clinical cardiologist Circulation 2002 105 : 546-549
10. Lerman A Zeicher N Endothelial function and cardiac events Circulation 2005 111 363-368
11. Fischer T Comment on the human vascular system(Hungarian) Orv Hetil 2006 147 : 1145
12. Marchesi C Ebrahimian T mAngulo O Obesity/Metabolic Syndrome : Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction Hypertension 2009 54 : 1384-1392
13. Yi L Chen CY Jin X Differential suppression of intracellular reactive oxygen species mediated signaling pathways in vascular endothelial cells by several subclasses of flavonoids Biochimie 2012 94 : 2035-2044
14. Colak F Majkik-Sikngh N Zoric L The impact of inflammation to the antioxidant defence parameters in AMD patients Aging Clin Exp Res 2012 24 ;588-594
15. Colak F Mojkie-Singh N Zoric L The role of CRP and inflammation in the pathogenesis of age related macular degeneration Biochem Med (Zagreb) 2012 22 : 39-48
16. Salminen A Kaupinnen A Hyttinen JM Endoplasmic reticulum stress in AMD:trigger for neovascularization Mol Med 2010 16 :535-544
17. Young PJ Koh CH Shim W Endothelial microparticles:missing link in endothelial dysfunction? Eur J Prev Cardiol 2013 20 496-512
18. Chroni GN Boulanger CM Simon A Endothelial microparticles in diseases Cell Tissue Res 2009 335 :143-151
19. Wu KH Tan AG Rochtchina E Circulating inflammatory markers and homeostatic factors in age related maculopathy:a population based case control study Invest Ophthalmol Vis Sci 2007 48 1983-1988
20. Vischer UM van Willebrand Factor,endothelial dysfunction and cardiovascular disease J thromb Haemost 2006 4 :1186-1193
21. Katherin CB Wing-Sun C Victor HG Advanced glycation endproducts and endothelial dysfunction in type 2 diabetes Diabetes Care 2002 25 :1055-1059
22. Evereklioglu C Doganay S Cekmen M Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age related macular degeneration Doc Ophthalmol 2003 106 :129-136
23. Hennig B Ching K Chow L Lipid peroxidation and endothelial cell injury Free Radic Biol Med 1988 4 :99-106
24. Adali E Kurdoglu M Adoli F The relationship between brachial artery flow mediated dilatation,high sensitivity CRP and uterine artery velocimetry with preeclampsia J Clin Ultrasound 2011 39 : 191-197
25. Cellini M Strobbe E Gizzi C Endothelin 1 plasma levels and vascular endothelial dysfunction in primary open angle galaucoma Life Sci 2012 91 :699-702
26. Morohoshi K Goodwin AM Obbayashi M Ono SJ Autoimmunity in retinal degeneration: autoimmune retinopathy and age related macular degeneration J Autoimmun 2009 33 : 247-254
27. Miller DM Espinosa-Heidmann DG Legra J The association orior cytomegalo virus infection with neovascular AMD Am J Ophthalmol 2004 138 :323-328
28. Brzozovska A Puchalska-Niedhal L Oral status as a potential source of infection in AMD patients-introduction Klin Oczna 2012 114 29-32
29. Jones JB Tao Y Neumaier M Monocyte chemotractant protein I,intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in exudative AMD Arch Ophthalmol 2010 128 : 1281-1284
30. Connell PP Keane PA O Neill EC Risk factors for age related maculopathy J Ophthalmol 2009 1-39 :360764. doi: 10.1155/2009/360764
31. Ikram MK Mitchell P Klien R Age related macular degeneration and long term risk of stroke subtypes Stroke 2012 43 : 1681-1683
32. Totan Y Cekin OS Borazan M Plasma malondialdehyde and nitric oxide levels in AMD Br J Ophthalmol 2001 85 :1426-1428
33. Xu W Grunwald JF Metelitsina TI Association of risk factors for choroidal neovascularization in AMD with decreased foveolar choroidal circulation Am J Ophthalmol 2010 150 : 40-47
34. Xia WH Li J Su C Physical exercise attenuates age associated reduction in endothelium repairative capacity of endothelial progenitor cells Ageing Cell 2012 11 : 111-119
35. Fischer T New possible strategy for prevention and preventive treatment of AMD resting on recent clinical and pathophysiological observations CEMED 2009 3 : 415-430
36. Shotliff K Duncan G Diabetes and the eye In,Shaw KM,Cummings MH(editors)Diabetic Complications 2005 Chichester UK, John Wiley & Sons p 1-19
37. Cheung N Wong TY Obesity and eye diseases Surv Ophthalmol 2007 52 : 180-195
38. Boulaumine A Marummo T Lefontan M Leptin induces oxidative stress in human endothelial cells FASEB J 1999 13 :1231-1238
39. Caldwell RB Bertoli M Behzadian MA Vascular endothelial growth factor and diabetic retinopathy:role of oxidative stress Curr Drug Targets 2005 6 : 511-524
40. Ambati J Ambati BK Yoo SH Age related macular degeneration :etiology,pathogenesis and therapeutic strategies Surv Ophthalmol 2003 48 : 257-293
41. Tagaki H Aging and retinal vascular diseases Nippon Ganka Gakkai Zasshi 2007 111 : 207-230
42. Chakravarthy U Wong TY Fitcher A Clinical risk factors for AMD:a systematic overview and meta analysis BMC Ophthalmol 2010 10:31. doi: 10.1186/1471-2415-10-31.
43. Pons m Marin-Castano ME Nicotine increases VEGF/PEDF ratio in retinal pigment epithelium:a possible mechanism for choroidal neovascularization in passive smokers with AMD Invest Ophthalmol Vis Sci 2011 52: 3842–3853.
44. Golbidi SD Laher I Exercise and the cardiovascular system Cardiol Res Pract 2012 article I d 210852
45. Willioms PT Prospective study of incident AMD in relation to vigourous physical activity during a seven year follow up Invest Ophthalmol Vis Sci 2009 50 101-106
46. Wong IYH Koo SCY Chan CWN Prevention of age related macular degeneration Int Ophthalmol 2011 31 :73-82
47. King RE Kent KD Bomser JA Resveratrol reduces oxidation and proliferation of human RPE cells via Erk (extracellular signal regulated kinase) inhibition Chem Biol Interac 2005 151 :143-149
48. Kijstra A Tuan Y Kelly ER Lutein :more than just a filter for blue light Prog Retin Eye Res 2012 31 : 303-315
49. Mares JA Voland RP Sondel SA Healthy lifestyle related to subsequent prevalence of age related macular degeneration Arch Ophthalmol 2011 129 :470- 480
50. Olea JL Aragon JA Zapata M Charecteristics of patients with wet AMD and low intake of lutein and zeaxanthin Arch Soc Esp Oftalmol 2012 87 :112-118
51. Uchiki T Weikel KA Jiao W Glycation altered proteolysis as a pathologic mechanism that links dietary glycaemic index,ageing and age related diseases(in non diabetics) Ageing cell 2012 11 1-13
52. Chiu CJ Taylor A Dietary hyperglycaemia,glycaemic index and metabolic retinal diseases Prog Retin Eye Res 2011 30 : 18-53
53. Peters A Magliano DJ Stevens J Changes in abdominal obesity and AMD::the atherosclerosis risk in communities study Arch Ophthalmol 2008 126 1554-1560
54. Anderson RM Weindruck R The calorie restriction paradigm :implications for healthy human ageing Am J Human Biol 2012 24:101-106
55. Augood C Chakravarthy U Young I Oily fish consumption , dietary DHEA and EPA intakes and association with neovascular AMD Am J Clin Nutr 2008 88 398-406
56. Millen AE Voland R Sondel SA Vitamin D status and early AMD in postmenopausal women Arch Ophthalmol 2011 129 : 481-489
57. Christe WG Glynn RJ Chew EY Folic acid,pyridoxine and cyanocobalamine combination treatment and AMD in women Arch Intern Med 2009 169 : 335-341
58. Prasad AS Zinc:an antioxidant and anti-inflammatory agent-role of zinc in degenerative diseases of ageing J Trace Elem Med Biol 2014;28:364-371
59. Semes LP Recent evidence points to common pathways in AMD and vascular disease:Research supports dietary modification or supplementation to reduce risk Primary Care Optometry News Feb 2012
60. Zampatti S Ricci F Cusumano A Marsella LT Novelli G Giardina E Review of nutrient actions on AMD Nutrition Research 2014 34 :95-105
61. Jablecka A Bagdanski P Balcer N The effect of oral L-arginine supplementation on fasting glucose,HbA1c,NO and total antioxidant status in diabetic patients with atherosclerotic peripheral vascular disease of lower extremities Eur Rev Med Pharmacol Sci 2012 16 : 342-350
62. Sharma A Bernatchez PN Targeting endothelial dysfunction in vascular complications associated with diabetes Int J Vasc Med 2012 :750126. doi: 10.1155/2012/750126
63. Blasi MA Bovina C Carella G Does coenzyme Q10 plays a role in opposing oxidative stress in patients with AMD? Ophthalmologia 2001 215 :51-54
64. Nakajima Y Inakuchi Y Bishi M Coenzyme Q10 protects retinal cells against oxidative stress in vivo and in vitro Brain Res 2008 1226 : 226-233-
65. Kubota S Kunhara T Ebinuma M Resveratrol prevents light induced retinal degeneration via suppressing activator protein 1 activation Am J Pathol 2010 177: 1725-1731
66. Lassalaletta AD Chu LM Elmadhun NY Cardioprotective effect of red wine and vodka in a model of endothelial dysfunction J Surg Res 2012 178 :586-592
67. Rastmanesh R Potential of melatonin to treat or prevent AMD through stimulation of telomerase activity Med Hypothes 2011 76 :79-85
68. Tai K Yu GP Chen M Urinary 6-sulphoxy melatonin level in AMD patients Mol Vis 2009 15 1673-1679
69. Muenzel T Gori T Nebivolol,the some what different beta blocker J Am ColL Cardiol 2009 54 :1491-1499
70. Kurihara T Ozhawa Y Ishida S Renin-angiotensin system hyperactivation can induce inflammation and retinal neural dysfunction Intern J Inflam 2012 ID 581695, 14 pages http://dx.doi.org/10.1155/2012/581695
71. Wight SA O Prey FM McHenry MT A randomized interventional trial of Omega-3 PUFA on endothelial function and disease activity in SLE Ann Rheum Dis 2008 68 : 841-848
72. Parshadsingh HA Moore DM PPAR gamma agonist:potential as therapeutics for neovascular retinopathies PPAR Res 2008;2008:164273. doi: 10.1155/2008/164273.
73. Lopez-Sendon J Swedberg K McMurray J Expert consensus document on angiotensin converting enzyme inhibitors in vascular disease Eur Heart J 2004 25 1454-1470
74. Ceriello A New insights on oxidative stress and diabetic complication may lead to a causal†antioxidant therapy Diabetes Care 2003 25 1589-1596
75. Molavi B Metha HL Oxidative stress in cardiovascular disease:molecular basis of its deleterious effect Curr Opin Cardiol 2004 19 :477-493
76. Asselberg FW van der Harst P Jessurum GAJ Clinical impact of vasomotor assessment and role of ACE inhibitors and AR Blockers Vasc Pharmacol 2005 42 125-140
77. Ota H Eto H Kano MR Induction of eNOS,SIRT1 and Catalase by statins,inhibits endothelial senescence through the Akt pathway Arterioscler Thromb Vasc Biol 2010 30 : 2205-2211
78. Hall NF Gale CR Sudall H Risk of macular degeneration in users of statins:cross sectional study BMJ 2001 323 : 375-376
79. Kim KJ Kim KS Kim NR Effects of simvastatin on the expression of heme oxygenase1 in human RPE cells Invest Ophthalmol Vis Sci 2012 53 : 6456-6464
80. Marianne S HMG-CoA inhibitors:Evaluation of the role and actions in AMD J Physiol Pathophysiol 2010 1 : 13-17
81. Moravietz H LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis Dtsch Med Wochenschr 2010 135 :308-312
82. Coyas A The efficacy of trimetazidine in cochleovestibular disorders of ischaemic origin : a crossover control versus placebo trial Annales d Otolaryngologe et d Chirurge 1990 1(suppl 1070:81-87
83. Wu TC Chen YH Leu H Carvedilol: a pharmacological antioxidant Free Radic Biol Med 2007 43 :1508-1522
84. Hwang J Kleinheunz DJ Rupnow HL The PPAR gamma ligand rossiglitazone reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice Vascul Pharmacol 2007 46 : 456-462
85. Ziemann SD Melenovsky V Clattenburg L Advanced glycation end product crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension J Hypertens 2007 25: 577-583
86. Thampl P Rao HV Mitter SK The 5HT1a receptor agonist 8-OH-DPAT induces protection from lipofuschin accumulation and oxidative stress in RPE PloS One 2012 7.e34468 DOI: 10.1371/journal.pone.0034468
87. Mirshaki A Hoehn R Lorenz K Anti-TNF alfa for retinal diseases: current knowledge and future concepts J Ophthalmic Vis Res 2012 7 : 39-44
88. Hora R Inomata Y Kawaji T Suppression of choroidal neovascularization by n-acetyl cystein in mice Curr Eye Res 2010 35 : 1012-1020
89. Rahrer B Long Q Coughlin B A targeted inhibitor of the alternative complement pathway reduces angiogenesis in mouse model of AMD Investig Ophthalmol Vis Sci 2009 50 : 3056-3064
90. WHO: VISION 2020:The Right to Sight-Global initiative for the elimination of avoidable blindness.Action Plan 2006-2011.Geneva WHO 2007
91. Gibson DM Diabetic retinopathy and age related macular degeneration in the US Am J Prev Med 2012 43 : 48-54
92. WHO Consultation Report. Public Health Management of Chronic Eye Diseases Geneva WHO Sept 2011
2. Voutilinen-Kaunisto RM Terasvirta ME Usirupa MIJ Age related macular degeneration in newly diagnosed type 2 diabetes patients and control subjects Diabetes Care 2000 23 1672-1678
3. Sander B, Larsen M Meldow B Diabetic macular oedema:passive and active transport of fluorescine through the blood retina barrier. Invest Ophthalmol Vis Sci 2001, 42:433-438.
4. Bhutto I, Lutty G Understanding age related macular degeneration(AMD):relationships between the photoreceptor/retinal pigment epithelium/Bruchs membrane/choriocapillaris complex Molecular Aspects of Medicine 2012 33:295-317
5. Machalinska A Kawa MP Marlicz WS Complement system activation and endothelial dysfunction in patients with age related macular degeneration:possible relation between AMD and atherosclerosis Acta Ophthalmol 2012 90 695-703
6. Machalinska A Dziedziejko V Mazolevska-Piotrovska K Elevated plasma levels of C3a complement compound in the exudative form of AMD Ophthalmic Res 2009 42 54-59
7. Reynolds R Hartnett ME Atkinson JP Plasma complement components and activation fragment associations with AMD genotypes and phenotypes Invest Ophthalmol Vis Sci 2009 50 5818-5827
8. Seddom JM Rifai M Association with C reactive protein and age related macular degeneration JAMA 2004 281 704-710
9. Verma S Anderson TJ Fundamentals of endothelial function for the clinical cardiologist Circulation 2002 105 : 546-549
10. Lerman A Zeicher N Endothelial function and cardiac events Circulation 2005 111 363-368
11. Fischer T Comment on the human vascular system(Hungarian) Orv Hetil 2006 147 : 1145
12. Marchesi C Ebrahimian T mAngulo O Obesity/Metabolic Syndrome : Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction Hypertension 2009 54 : 1384-1392
13. Yi L Chen CY Jin X Differential suppression of intracellular reactive oxygen species mediated signaling pathways in vascular endothelial cells by several subclasses of flavonoids Biochimie 2012 94 : 2035-2044
14. Colak F Majkik-Sikngh N Zoric L The impact of inflammation to the antioxidant defence parameters in AMD patients Aging Clin Exp Res 2012 24 ;588-594
15. Colak F Mojkie-Singh N Zoric L The role of CRP and inflammation in the pathogenesis of age related macular degeneration Biochem Med (Zagreb) 2012 22 : 39-48
16. Salminen A Kaupinnen A Hyttinen JM Endoplasmic reticulum stress in AMD:trigger for neovascularization Mol Med 2010 16 :535-544
17. Young PJ Koh CH Shim W Endothelial microparticles:missing link in endothelial dysfunction? Eur J Prev Cardiol 2013 20 496-512
18. Chroni GN Boulanger CM Simon A Endothelial microparticles in diseases Cell Tissue Res 2009 335 :143-151
19. Wu KH Tan AG Rochtchina E Circulating inflammatory markers and homeostatic factors in age related maculopathy:a population based case control study Invest Ophthalmol Vis Sci 2007 48 1983-1988
20. Vischer UM van Willebrand Factor,endothelial dysfunction and cardiovascular disease J thromb Haemost 2006 4 :1186-1193
21. Katherin CB Wing-Sun C Victor HG Advanced glycation endproducts and endothelial dysfunction in type 2 diabetes Diabetes Care 2002 25 :1055-1059
22. Evereklioglu C Doganay S Cekmen M Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age related macular degeneration Doc Ophthalmol 2003 106 :129-136
23. Hennig B Ching K Chow L Lipid peroxidation and endothelial cell injury Free Radic Biol Med 1988 4 :99-106
24. Adali E Kurdoglu M Adoli F The relationship between brachial artery flow mediated dilatation,high sensitivity CRP and uterine artery velocimetry with preeclampsia J Clin Ultrasound 2011 39 : 191-197
25. Cellini M Strobbe E Gizzi C Endothelin 1 plasma levels and vascular endothelial dysfunction in primary open angle galaucoma Life Sci 2012 91 :699-702
26. Morohoshi K Goodwin AM Obbayashi M Ono SJ Autoimmunity in retinal degeneration: autoimmune retinopathy and age related macular degeneration J Autoimmun 2009 33 : 247-254
27. Miller DM Espinosa-Heidmann DG Legra J The association orior cytomegalo virus infection with neovascular AMD Am J Ophthalmol 2004 138 :323-328
28. Brzozovska A Puchalska-Niedhal L Oral status as a potential source of infection in AMD patients-introduction Klin Oczna 2012 114 29-32
29. Jones JB Tao Y Neumaier M Monocyte chemotractant protein I,intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in exudative AMD Arch Ophthalmol 2010 128 : 1281-1284
30. Connell PP Keane PA O Neill EC Risk factors for age related maculopathy J Ophthalmol 2009 1-39 :360764. doi: 10.1155/2009/360764
31. Ikram MK Mitchell P Klien R Age related macular degeneration and long term risk of stroke subtypes Stroke 2012 43 : 1681-1683
32. Totan Y Cekin OS Borazan M Plasma malondialdehyde and nitric oxide levels in AMD Br J Ophthalmol 2001 85 :1426-1428
33. Xu W Grunwald JF Metelitsina TI Association of risk factors for choroidal neovascularization in AMD with decreased foveolar choroidal circulation Am J Ophthalmol 2010 150 : 40-47
34. Xia WH Li J Su C Physical exercise attenuates age associated reduction in endothelium repairative capacity of endothelial progenitor cells Ageing Cell 2012 11 : 111-119
35. Fischer T New possible strategy for prevention and preventive treatment of AMD resting on recent clinical and pathophysiological observations CEMED 2009 3 : 415-430
36. Shotliff K Duncan G Diabetes and the eye In,Shaw KM,Cummings MH(editors)Diabetic Complications 2005 Chichester UK, John Wiley & Sons p 1-19
37. Cheung N Wong TY Obesity and eye diseases Surv Ophthalmol 2007 52 : 180-195
38. Boulaumine A Marummo T Lefontan M Leptin induces oxidative stress in human endothelial cells FASEB J 1999 13 :1231-1238
39. Caldwell RB Bertoli M Behzadian MA Vascular endothelial growth factor and diabetic retinopathy:role of oxidative stress Curr Drug Targets 2005 6 : 511-524
40. Ambati J Ambati BK Yoo SH Age related macular degeneration :etiology,pathogenesis and therapeutic strategies Surv Ophthalmol 2003 48 : 257-293
41. Tagaki H Aging and retinal vascular diseases Nippon Ganka Gakkai Zasshi 2007 111 : 207-230
42. Chakravarthy U Wong TY Fitcher A Clinical risk factors for AMD:a systematic overview and meta analysis BMC Ophthalmol 2010 10:31. doi: 10.1186/1471-2415-10-31.
43. Pons m Marin-Castano ME Nicotine increases VEGF/PEDF ratio in retinal pigment epithelium:a possible mechanism for choroidal neovascularization in passive smokers with AMD Invest Ophthalmol Vis Sci 2011 52: 3842–3853.
44. Golbidi SD Laher I Exercise and the cardiovascular system Cardiol Res Pract 2012 article I d 210852
45. Willioms PT Prospective study of incident AMD in relation to vigourous physical activity during a seven year follow up Invest Ophthalmol Vis Sci 2009 50 101-106
46. Wong IYH Koo SCY Chan CWN Prevention of age related macular degeneration Int Ophthalmol 2011 31 :73-82
47. King RE Kent KD Bomser JA Resveratrol reduces oxidation and proliferation of human RPE cells via Erk (extracellular signal regulated kinase) inhibition Chem Biol Interac 2005 151 :143-149
48. Kijstra A Tuan Y Kelly ER Lutein :more than just a filter for blue light Prog Retin Eye Res 2012 31 : 303-315
49. Mares JA Voland RP Sondel SA Healthy lifestyle related to subsequent prevalence of age related macular degeneration Arch Ophthalmol 2011 129 :470- 480
50. Olea JL Aragon JA Zapata M Charecteristics of patients with wet AMD and low intake of lutein and zeaxanthin Arch Soc Esp Oftalmol 2012 87 :112-118
51. Uchiki T Weikel KA Jiao W Glycation altered proteolysis as a pathologic mechanism that links dietary glycaemic index,ageing and age related diseases(in non diabetics) Ageing cell 2012 11 1-13
52. Chiu CJ Taylor A Dietary hyperglycaemia,glycaemic index and metabolic retinal diseases Prog Retin Eye Res 2011 30 : 18-53
53. Peters A Magliano DJ Stevens J Changes in abdominal obesity and AMD::the atherosclerosis risk in communities study Arch Ophthalmol 2008 126 1554-1560
54. Anderson RM Weindruck R The calorie restriction paradigm :implications for healthy human ageing Am J Human Biol 2012 24:101-106
55. Augood C Chakravarthy U Young I Oily fish consumption , dietary DHEA and EPA intakes and association with neovascular AMD Am J Clin Nutr 2008 88 398-406
56. Millen AE Voland R Sondel SA Vitamin D status and early AMD in postmenopausal women Arch Ophthalmol 2011 129 : 481-489
57. Christe WG Glynn RJ Chew EY Folic acid,pyridoxine and cyanocobalamine combination treatment and AMD in women Arch Intern Med 2009 169 : 335-341
58. Prasad AS Zinc:an antioxidant and anti-inflammatory agent-role of zinc in degenerative diseases of ageing J Trace Elem Med Biol 2014;28:364-371
59. Semes LP Recent evidence points to common pathways in AMD and vascular disease:Research supports dietary modification or supplementation to reduce risk Primary Care Optometry News Feb 2012
60. Zampatti S Ricci F Cusumano A Marsella LT Novelli G Giardina E Review of nutrient actions on AMD Nutrition Research 2014 34 :95-105
61. Jablecka A Bagdanski P Balcer N The effect of oral L-arginine supplementation on fasting glucose,HbA1c,NO and total antioxidant status in diabetic patients with atherosclerotic peripheral vascular disease of lower extremities Eur Rev Med Pharmacol Sci 2012 16 : 342-350
62. Sharma A Bernatchez PN Targeting endothelial dysfunction in vascular complications associated with diabetes Int J Vasc Med 2012 :750126. doi: 10.1155/2012/750126
63. Blasi MA Bovina C Carella G Does coenzyme Q10 plays a role in opposing oxidative stress in patients with AMD? Ophthalmologia 2001 215 :51-54
64. Nakajima Y Inakuchi Y Bishi M Coenzyme Q10 protects retinal cells against oxidative stress in vivo and in vitro Brain Res 2008 1226 : 226-233-
65. Kubota S Kunhara T Ebinuma M Resveratrol prevents light induced retinal degeneration via suppressing activator protein 1 activation Am J Pathol 2010 177: 1725-1731
66. Lassalaletta AD Chu LM Elmadhun NY Cardioprotective effect of red wine and vodka in a model of endothelial dysfunction J Surg Res 2012 178 :586-592
67. Rastmanesh R Potential of melatonin to treat or prevent AMD through stimulation of telomerase activity Med Hypothes 2011 76 :79-85
68. Tai K Yu GP Chen M Urinary 6-sulphoxy melatonin level in AMD patients Mol Vis 2009 15 1673-1679
69. Muenzel T Gori T Nebivolol,the some what different beta blocker J Am ColL Cardiol 2009 54 :1491-1499
70. Kurihara T Ozhawa Y Ishida S Renin-angiotensin system hyperactivation can induce inflammation and retinal neural dysfunction Intern J Inflam 2012 ID 581695, 14 pages http://dx.doi.org/10.1155/2012/581695
71. Wight SA O Prey FM McHenry MT A randomized interventional trial of Omega-3 PUFA on endothelial function and disease activity in SLE Ann Rheum Dis 2008 68 : 841-848
72. Parshadsingh HA Moore DM PPAR gamma agonist:potential as therapeutics for neovascular retinopathies PPAR Res 2008;2008:164273. doi: 10.1155/2008/164273.
73. Lopez-Sendon J Swedberg K McMurray J Expert consensus document on angiotensin converting enzyme inhibitors in vascular disease Eur Heart J 2004 25 1454-1470
74. Ceriello A New insights on oxidative stress and diabetic complication may lead to a causal†antioxidant therapy Diabetes Care 2003 25 1589-1596
75. Molavi B Metha HL Oxidative stress in cardiovascular disease:molecular basis of its deleterious effect Curr Opin Cardiol 2004 19 :477-493
76. Asselberg FW van der Harst P Jessurum GAJ Clinical impact of vasomotor assessment and role of ACE inhibitors and AR Blockers Vasc Pharmacol 2005 42 125-140
77. Ota H Eto H Kano MR Induction of eNOS,SIRT1 and Catalase by statins,inhibits endothelial senescence through the Akt pathway Arterioscler Thromb Vasc Biol 2010 30 : 2205-2211
78. Hall NF Gale CR Sudall H Risk of macular degeneration in users of statins:cross sectional study BMJ 2001 323 : 375-376
79. Kim KJ Kim KS Kim NR Effects of simvastatin on the expression of heme oxygenase1 in human RPE cells Invest Ophthalmol Vis Sci 2012 53 : 6456-6464
80. Marianne S HMG-CoA inhibitors:Evaluation of the role and actions in AMD J Physiol Pathophysiol 2010 1 : 13-17
81. Moravietz H LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis Dtsch Med Wochenschr 2010 135 :308-312
82. Coyas A The efficacy of trimetazidine in cochleovestibular disorders of ischaemic origin : a crossover control versus placebo trial Annales d Otolaryngologe et d Chirurge 1990 1(suppl 1070:81-87
83. Wu TC Chen YH Leu H Carvedilol: a pharmacological antioxidant Free Radic Biol Med 2007 43 :1508-1522
84. Hwang J Kleinheunz DJ Rupnow HL The PPAR gamma ligand rossiglitazone reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice Vascul Pharmacol 2007 46 : 456-462
85. Ziemann SD Melenovsky V Clattenburg L Advanced glycation end product crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension J Hypertens 2007 25: 577-583
86. Thampl P Rao HV Mitter SK The 5HT1a receptor agonist 8-OH-DPAT induces protection from lipofuschin accumulation and oxidative stress in RPE PloS One 2012 7.e34468 DOI: 10.1371/journal.pone.0034468
87. Mirshaki A Hoehn R Lorenz K Anti-TNF alfa for retinal diseases: current knowledge and future concepts J Ophthalmic Vis Res 2012 7 : 39-44
88. Hora R Inomata Y Kawaji T Suppression of choroidal neovascularization by n-acetyl cystein in mice Curr Eye Res 2010 35 : 1012-1020
89. Rahrer B Long Q Coughlin B A targeted inhibitor of the alternative complement pathway reduces angiogenesis in mouse model of AMD Investig Ophthalmol Vis Sci 2009 50 : 3056-3064
90. WHO: VISION 2020:The Right to Sight-Global initiative for the elimination of avoidable blindness.Action Plan 2006-2011.Geneva WHO 2007
91. Gibson DM Diabetic retinopathy and age related macular degeneration in the US Am J Prev Med 2012 43 : 48-54
92. WHO Consultation Report. Public Health Management of Chronic Eye Diseases Geneva WHO Sept 2011
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Pandit, A., Bahuguna, D. P., Pandey, A. K., & Pandey, B. L. (2016). Retinal Inflammaging: Pathogenesis and Prevention. Innovare Journal of Medical Sciences, 4(4), 1-5. Retrieved from https://innovareacademics.in/journals/index.php/ijms/article/view/13280
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