Search for other papers by Tamás Fischer in
Current site
Google Scholar
PubMed
Abstract
In the genesis and later development of age-related macular degeneration (AMD), endothelial dysfunction (ED) has a crucial role. Various medicines (ACE inhibitors, AR blockers, statins, acetylsalicylic acid, trimetazidine, and third generation beta blockers) exert a beneficial effect on endothelial dysfunction or its consequential functional, structural and metabolic disorders. The beneficial effect of a favourable influence on and successful treatment of ED in patients with chronic vascular and cardiovascular diseases has become evidence now. In ED induced by oxidative stress (OS) ACE inhibitors, AR blockers and statins regenerate the lost balance between vasoconstrictors and vasodilators, growth factors and their inhibitors, pro-inflammatory and anti-inflammatory agents, as well as pro-thrombotic and fibrinolytic factors. They inhibit the development of OS and the evolution of its harmful effects. In addition, the AT1-receptor blocker telmisartan, with its peroxisome proliferator-activated receptor-gamma (PPARγ) agonist effect, also inhibits the development of choroidal neovascularisation (CNV); it exerts a clinically favourable influence on CNV and improves it. Aspirin, with its pleiotropic antiplatelet activity, effectively contributes to the restoration of the balance of endothelium, and trimetazidine helps in normalising, restoring the pathological metabolic status of organ tissues with impaired function. The third generation beta blocker carvedilol, nebivolol, as well as the PPARγ agonist pioglitazone and rosiglitazone exert their protective vascular effects exactly by means of their mitochondrial antioxidant effects. As the human vascular system is uniform, consubstantial; thus medicines beneficial in ED exert a favourable effect also on the vessels of the eye, in the retina. Based on the above, it seems logical to presume that, as a part of our primary and secondary preventive activity, such medicines should be given to (1) patients who have no macular degeneration, but have risk factors of AMD [and cardiovascular (CV) disease] inducing ED, and are older than 50 years; (2) patients who have been diagnosed with unilateral AMD, in order to prevent the damage of the contralateral eye due to macular degeneration; and finally (3) patients who have been diagnosed with bilateral AMD, in order to avert deterioration and in the hope of a potential improvement. In addition, we should strive to completely eliminate the risk factors of macular degeneration (and CV disease) which induce OS and consequential ED.
“A novel interpretation of relations between phenomena, particularly if it is a source for intellectual value, is worth as much as a discovery”
Confucius
-
[1]. G. Donat C. Pournaras J. L. Munoz et al.1995 Nitric oxide controls alveolar tone in the retina of the miniature pig Invest. Ophthalmol. Vis. Sci. 36 2228–2237.
-
[2]. I. O. Haefliger J. Flammer T. F. Lüscher 1993 Endothelium-dependent regulation in ophthalmic and ciliary arteries Invest. Ophthalmol. Vis. Sci. 34 1772.
-
[3]. P. Meyer J. Flammer T. F. Lüschner 1993 Endothelium-dependent regulation of the ophtahalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelin Invest. Ophthalmol. Vis. Sci. 34 3614–21.
-
[4]. I. O. Haefliger P. Meyer J. Flammer et al.1994 The vascular endothelium as a regulator of the circulation in the eye: a new concept in ophthalmology Arch. Ophthalmol. 39 123–132.
-
[5]. G. Y. H. Lip A. Blann M. Hope-Ross et al.2001 Age-related macular degeneration is associated with increased vascular endothelial goss factor, hemorrheology and endothelial dysfunction Ophthalmology 108 705–710.
-
[6]. G. Malukiewitz-Wisniewska D. Rose 2005 von Willebrand facor in plasma of patinets with age related macular degeneration Klin. Oczna 107 70–72.
-
[7]. T. Fischer 2004 Über die medikamentöse Praevention und die praeventive Behandlung der altersbedingten Makuladegeneration (AMD) durch die günstige Beeinflussung der Gefaeßen — dotheldysfunktion (ED) Klin. Monatsbl. Augenkeilkd. 221 1062.
-
[8]. T. Fischer 2008 Az időskori maculadegeneratio gyógyszeres megelőzésének és preventív kezelésének lehetséges új stratégiája Orv. Hetil. 149 121–127 (New possible strategy of the medicinal prevention and preventive treatment in age-related macular degeneration.).
-
[9]. S. Verma T. J. Anderson 2002 Fundamentals of endothelial function for the clinical cardiologist Circulation 105 546–549.
-
[10]. A. Lerman N. Zeicher 2005 Endothelial function Cardiac events. Circulation 111 363–368.
-
[11]. T. Fischer 2006 Referensi megjegyzés a humán érrendszer részeinek egylényegűségéről Orv. Hetil. 147 1145 (Comment to the human vascular system.).
-
[12]. A. M. Heagerty 2004 Effect of AT1-receptor blockade on vascular structure and function Eur. Heart J. 6 Suppl.H H17–H21.
-
[13]. Jackson, E. K.: Renin and angiotensin: drugs affecting renal and cardiovascular function. In: Goodman and Gilman's Pharmacologic Basis of Therapeutics. Ed.: Brunton, L. L., Lazo, J. S., Parker, K. L., McGraw-Hill, N.Y., 2005, 789–808.
-
[14]. K. K. Koh Y. Y. Abn S. H. Han et al.2003 Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients J. Am. Coll. Cardiol. 42 905–910.
-
[15]. E. Lonn H. C. Gerstein M. Smieja et al.2003 Mechanism of cardiovascular risk reduction of ACE inhibitor ramipril: insights from HOPE and HOPE substudies Eur. Heart J. 5 Suppl.A A43–A48.
-
[16]. O. Soehnlein A. Schmeisser J. Cicho et al.2005 ACE inhibition lowers angiotensin-II-induces monocyte ahesion to HUVEC by reduction of p65 translocation and ATI expression J. Vasc. Res. 42 399–407.
-
[17]. Task Force of ACE-Is of European Society of Cardiology 2004 Expert consensus document on angiotensin converting enzyme inhibitor in vascular disease Eur. Heart J. 25 1454–1470.
-
[18]. S. Wassman G. Nickenig 2004 The role of AT1-receptor in the cardiovascular continuum Eur. Heart J. 6 Suppl.H H3–H9.
-
[19]. S. Wassman N. Laufs A. T. Bauner et al.2001 Inhibition of geranygeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells Mol. Pharmacol 59 649–654.
-
[20]. M. Landmesser D. G. Harrison 2001 Oxidant stress as a marker for cardiovascular events Ox marks the spot. Circulation 104 2638–2640.
-
[21]. R. Ferrari G. Guardigli 2004 Angiotensin II overproduction: enemy of the vascular wall Eur. Heart J. 4 SupplA A26–A30.
-
[22]. N. Nagai Y. Oike K. I. Nagai et al.2006 Angiotensin II type receptor-mediated inflammation is required for choroidal neovascularisation Arterioscler. Thromb. Vasc. Biol. 26 2252–2259.
-
[23]. H.A. Pershadsingh D.M. Moore 2008 PPAR gamma agonist: Potential therapeutics for neovascular retinopathies PPAR Res. 2008 164–273.
-
[24]. A. Ceriello 2003 New insights on oxidative stress and diabetic complication may lead to a “causal” antioxidant therapy Diabetes Care 25 1589–1596.
-
[25]. B. Molavi H. L. Metha 2004 Oxidative stress in cardiovascular disease: molecular basis of its deleterious effect, its detection, and therapeutic consideration Curr. Opin. Cardiol. 19 477–493.
-
[26]. F. W. Asselberg P. van der Harst G. A. J. Jessurum et al.2005 Clinical impact of vasomotor assessment and role of ACE-inhibitors and AR-blockers Vasc. Pharmacol. 42 125–140.
-
[27]. R. S. McKelvie S. Yusuf D. Pericak et al.1999 Comparison of candesartan, enalapril, and their combination in congestive heart failure Circulation 100 1056–1064.
-
[28]. J. McMurray S. Solomon K. Piepera et al.2006 The effect of valsartan, captopril or both on arteriosclerotic events after acute myocardial infarction J. Am. Coll. Cardiol. 47 726–733.
-
[29]. K. Almutti R. Rimawi D. Spevack et al.2006 Effects of statins beyond lipid lowering: Potential for clinical benefits Internat. J. Cardiol. 109 7–15.
-
[30]. N.F. Hall C.R. Gale H. Sudall et al.2001 Risk of macular degeneration in users of statins: crosssectional study BMJ 323 375–376.
-
[31]. J. K. Liao U. Laufs 2005 Pleiotropic effects of statins Annu. Rev. Pharmacol. Toxicol. 45 89–118.
-
[32]. M. Minoru Y. Atachi H. Yamada et al.2004 Chorioidal neovascularisation is provided by bone marrow cells Stem. Cells 22 21–26.
-
[33]. S. E. Niessen E. M. Tuzcu T. Crowe et al.2005 Statin-therapy, LDL cholesterol, C-reactive protein, and coronary artery disease N. Eng. J. Med. 352 28–38.
-
[34]. K. Ray C. D. Cannon 2005 The potential relevance of the multiple lipid-indpendent (pleiotropic) effects of the statins J. Am. Coll. Cardiol. 46 1425–1433.
-
[35]. M. E. Wydlanski N. Gokce J. E. Keanea et al.2003 The clinical implication of endothelial dysfunction J. Am. Coll. Cardiol. 42 1149–1160.
-
[36]. M. Honjo H. Tanihara K. Nishijima et al.2002 Statins inhibit leukocyte-endothelial interaction and prevent neuronal death induced by ischemia-reperfusion injury in the rat retina Arch. Ophthalmol. 120 1707–1713.
-
[37]. W. Palinsky S. Tsimiskas 2002 Immunomodulatory effects of statins J. Am. Soc. Nephrol. 13 1673–1681.
-
[38]. G. McGwin C. Owsley C. A. Curcio et al.2003 The association between statin use and age related macular degeneration Br. J. Ophthalmol. 87 1121–1125.
-
[39]. R. Wu D. Lamontagne J. Champlain et al.2002 Anti-oxidative properties of acetylsalicylic acid on vascular tissues from rats Circulation 105 387–392.
-
[40]. R. Wu M. Laplante J. Champlain et al.2004 Prevention of angiotensin-II-induced oxidative stress, hypertension and cardiovascular hypertrophy by acetylsalicylic acid J. Hypertens. 22 797–801.
-
[41]. A. Coyas 1990 The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial Annales d'Oto-Larygologe et de Chirurge Cervico-Faciale 1 107Suppl 81–87.
-
[42]. R. Belardinelli M. Solenghi L. Volpe et al.2007 Trimetazidine improves endothelial dysfunction: an antioxidant effect Eur. Heart J. 28 1102–1108.
-
[43]. C. Vitalem M. Wajngaten B. Sposato et al.2004 Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease Eur. Heart J. 25 1814–1821.
-
[44]. Országos Gyógyszerészeti Intézet 2002 Gyógyszer Kompendium. (National Pharmaceutical Institute: Drug Compendium.) MediMedia Információs Kft. Budapest 75.
-
[45]. K. Kaszuba-Bartkowiak M.S. Nowak P. Jurowsky et al.2007 The role of trimetazidine in the protection of the retina Arch. Med. Sci. 3 S65–S66.
-
[46]. T.C. Wu Y.H. Chen H. Leu et al.2007 Carvedilol, a pharmacological antioxidant Free Rad. Biol. Med. 43 1508–1522.
-
[47]. J. Hwang D. J. Kleinheinz H. L. Rupnow et al.2007 The PPARgamma ligand, rosiglitazone, reduce vascular oxidative stress and NADPH oxidase expression in diabetic mice Vasc. Pharmacol. 476 456–462.
-
[48]. J. M. Seddom N. Rifai 2004 Association with C-reactive protein and age-related macular degeneration JAMA 281 704–710.
-
[49]. D. D. Desoriet C. C. Klavier J. C. Witteman et al.2006 Complement factor H plymorphism, complement activators and risk of age-related macular degeneration JAMA 286 301–309.
-
[50]. A. Wachter Y. Sun B. Dasch et al.2004 Münster age- and retina study (MARCH). Association between risk factors for arteriosclerosis and age-related macular degeneration Ophthalmologe 101 1 50–53.
-
[51]. S. Fichtlscherer S. Breuer V. Schaehinger et al.2004 C-rective protein levels determine systemic nitric oxide bioavailability Eur. Heart J. 25 1412–1415.
-
[52]. M. J. Kern 2005 Conditions associated with impaired endothelial function, and surrogate soluble markers of endothelial dysfunction D. P. Zipes P. Libby R. O. Bonow E. Brauwald Brauwald's Heart Disease Elsevier-Saunders Philadelphia 1108–1109.
-
[53]. S. Verma P. E. Szmitko P. M. Ridker 2005 C-reactive protein comes of age Nat. Clin. Pract. Cardiovasc. Med. 2 29–36.
-
[54]. B. F. Becker B. Heindl C. Kupatt et al.2000 Endothelial function and hemostasis Zeitschrift Kardiol. 89 160–170.
-
[55]. G. Y. H. Lip A. Blann 1997 von Willebrand factor: a marker of endothelial dysfunction in vascular disorder? Cardiovasc. Res. 34 255–265.
-
[56]. T. Nagoaka L. Kuo Y. Ren et al.2008 C-reactive protein inhibits endothelium-dependent nitric oxide-mediated dilatation of retinal arterioles via enhanced superoxide production Invest. Ophthalmol. Vis. Sci. 49 5 2053–2060.
-
[57]. T. Radovits 2008 Új antioxidáns stratégiák időskori cardiovascularis diszfunkció kezelésében Orv. Hetil. 149 2377–2385 (New antioxidant strategy in the age associated cardiovascular dysfunction.).
-
[58]. S. Kaushic J.J. Wang V. Flood et al.2008 Dietary glycemic index and the risk of age-related macular degeneration Am. J. Clin. Nutr. 88 4 1104–1110.
-
[59]. S. Beatty D. Henson M. Boulton et al.2000 The role of oxidative stress in the pathogenesis of agerelated macular degeneration Survey Ophthalmol. 45 115–134.
-
[60]. S. Judge C. Leeuvenburgh 2007 Cardiac mitochondrial bioenergetics, oxidative stress, and aging Am. J. Physiol. Cell Physiol. 292 C1983–C1992.
-
[61]. P. L. Penfold M. C. Matigan M. C. Gillies et al.2001 Immunological and aetiological aspects of macular degeneration Progr. Retinal Eye Res. 20 385–415.
-
[62]. Gy. Salacz 1999 A látást befolyásoló degeneratív betegségek Orv. Hetil. 140 1507–1511 (Degenerative disease influencing the vision.).
-
[63]. J. M. Seddom B. Rosner S. George et al.2003 Progression of age-related macular degeneration. Association with body mass index, wirst circumference, and waist-hip ratio Arch Ophthalmol. 121 785–792.
-
[64]. S. C. Tomany R. Leenwen R. Klein et al.2004 Risk factors for incident age-related macular degeneration Ophthalmology 111 1280–1287.
-
[65]. R. E. Hogg J. V. Woodside S. E. Gilchrist et al.2008 Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularisation Ophthalmol. 115 6 1046–1052.
-
[66]. T. Ikeda H. Obayashi G. Hasegawa et al.2001 Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as risk factors for age-related macular degeneration Am. J. Ophthalmol. 132 191–195.
-
[67]. W. Smith P. Mitchell S. R. Leeder et al.1998 Plasma fibrinogen levels. Other cardiovasculart risk factors, and age-related macular degeneration The Blue Mountains Eye Study. Arch. Ophthalmol. 116 583–587.
-
[68]. R. Axer-Siegel D. Boura R. Ehrlich et al.2004 Association of neovascular macular degeneration and hyperhomocysteinemia Am. J. Ophtalmol. 137 84–89.
-
[69]. R. Klein B. Klein S. C. Tomaní et al.2003 Association of obstructive emphysema, gout, and inflammatory markers with long-term incidence of age-related macular maculopathy Arch. Ophthalmol. 121 674–678.
-
[70]. E. Sato G. T. Feke E. Y. Appelbaum et al.2006 Association between systemic arterial stiffness and age-related macular degeneration Graefes Arch. Clin. Exp. Ophthalmol. 244 963–971.
-
[71]. K. B. Beckman B. M. Ames 1998 The free radical theories of aging Physiol. Rev. 78 547–581.
-
[72]. W. Dröge 1995 Free radicals in the physiological control of cell function Progr. Cardiovasc. Dis. 378 129–154.
-
[73]. D. G. Greene M. J. Stevens I. Obrosova et al.1999 Glucose-induced oxidative stress and programmed cell death in diabetes mellitus Eur. J. Pharmacol. 375 217–223.
-
[74]. J. V. Keaney J. A. Vita 1995 Oxidative stress, and antioxidant protection in endothelium-derived relaxing factor action Prog. Cardiovasc. Dis. 378 129–154.
-
[75]. M. Valgimigli N. Merli D. Malgutt et al.2003 Endothelial dysfunction: Evidence for pathogenetic role of oxidative stress Arch. Biochem. Biophysics 420 255–261.
-
[76]. N. Basso N. Paglia J. Stella et al.2005 Protective effect of inhibition of the renin-angiotensin system on aging and oxidative stress Regulatoriy Peptides 128 247–252.
-
[77]. B. Hanig U. Landmesser C. Kahler et al.2001 Comparative effect of ACE inhibitor and angiotensin II type I receptor antagonism on bioavailability of nitric oxide: role of superoxide dysmutase Circulation 103 799–805.
-
[78]. A. J. Augustin J. Dick J. Offermann et al.2002 Bedeutung oxidativer Mechanismen bei Erkrankungen der Netzhaut Klin. Monatsbl. Augenheilkd. 219 631–643.
-
[79]. H. Cai D. G. Harrison 2000 Endothelial dysfunction in cardiovascular disease. The role of oxidative stress Circ. Res. 87 840–844.
-
[80]. E. Németh J. Feher V. Nagy et al.2006 Antioxidánsok szerepe a prevencióban Orv. Hetil. 25 1589–1596 (The role of antioxidants in the prevention.).
-
[81]. T. Fischer 2008 Érendothel-m ködészavar, oxidatív stressz: újabb tárgykörrel bővül az Orvosi Hetilap folyóirat-referáló rovata Orv. Hetil. 149 1323–1327 (Vascular dysfunction, oxidative stress: Newer topic in the Hungarian Medical Journal [Orvosi Hetilap].).
-
[82]. Herzlich, A. A., Jingsheng Tuo, Chi-Chao Chan: Peroxisome proliferator-activated receptor and age-related macular degeneration. Hindavi Publishing Corporation, PPAR Research, Volume 2008, Article ID; doi: 10.1155/2008/389507.
-
[83]. M. D. Cheitlin 2004 Erectile dysfunction: the earliest sign of generalized vascular disease? J. Am. Coll. Cardiol. 43 185–186.
-
[84]. D. R. Kaiser K. Billups C. Mason et al.2004 Impaired brachial artery endothelium dependent and -independent vasodilatation in men with erectile dysfunction and no other clinical cardiovascular disease J. Am. Coll. Cardiol. 43 179–184.
-
[85]. P. V. Targonski P. O. Bonetti G. M. Pumper et al.2003 Coronary endothelial dysunction is associated with an increased risk of cerebrovascular events Circulation 107 2805–2809.
-
[86]. T. Voutilainen-Kaunisto M. I. Uusitupa M. E. Terasvirta et al.2000 Age-related macular degeneration in newly diagnosed type 2 diabetic patients and control subjects Diabetes Care 23 1672–1678.
-
[87]. M.D. Knudtson R. Klein B.R. Klein 2006 Physical activity and the 15-year cumulative incidence of age-related macular degeneration: the Baever Dam Eye Study Br. J. Ophthalmol. 90 12 1461–1463.
-
[88]. T. Koto N. Nagai H. Mochimaru et al.2007 Eicosapentaenoic acid is anti-inflammatory in preventing chorioidal neovascularisation in mice Invest. Ophthalmol. Vis. Sci. 48 4328–4334.
-
[89]. C. Augood U. Chakravarthy I. Young et al.2008 Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and association with neovascular age-related macular degeneration Am. J. Clin. Nutr. 88 2 398–406.
| Clinical and Experimental Medical Journal | |
|---|---|
| Language | English |
| Size | |
| Year of Foundation |
2007 |
| Publication Programme |
ceased |
| Volumes per Year |
|
| Issues per Year |
|
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245 |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2060-6249 (Print) |
| ISSN | 2060-968X (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Nov 2024 | 86 | 0 | 0 |
| Dec 2024 | 26 | 0 | 0 |
| Jan 2025 | 39 | 0 | 0 |
| Feb 2025 | 58 | 0 | 0 |
| Mar 2025 | 70 | 0 | 0 |
| Apr 2025 | 28 | 0 | 0 |
| May 2025 | 5 | 0 | 0 |
1st Congress of Fatty Liver and Metabolic Syndrome
From Basic Science to the Clinical Praxis
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.