Author: Tamás Fischer
View More View Less
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $1,070.00

Absztrakt

A szem struktúráit vérrel ellátó érendothelium működészavarának kulcsfontosságú szerepe van az időskori maculadegeneráció létrejöttében. Az időskori maculadegeneráció érbetegség, végső soron az egész érrendszer megbetegedésének a része. Az endotheldiszfunkció helyreállítása megakadályozza az érbántalom és így az időskori maculadegeneráció kialakulását, vagy csökkenti a már kialakult elváltozást. A kockázati tényezők jelenlétében kialakuló endotheldiszfunkció és következményes időskori maculadegeneráció kiküszöbölésére, megelőzésére, illetve kezelésére nem gyógyszeres és gyógyszeres lehetőségek állnak rendelkezésre. Jelen dolgozat a gyógyszeres intervenciót taglalja. Ezek közé tartoznak a renin-angiotenzin rendszert gátló angiotenzinkonvertálóenzim-gátlók, angiotenzinreceptor-blokkolók és renininhibitorok, statinok, acetilszalicilsav, trimetazidin, harmadik generációs béta-blokkolók, peroxiszómaproliferátor-aktivált receptor-gamma-agonisták, folsav, D-vitamin, melatonin, az előrehaladt glikációs végtermékek keresztkötéseit feltörő alagebrium, az endothelinreceptor-antagonista bosentan, koenzim Q10, „kauzális” antioxidáns vitaminok, rezveratrol, L-arginin, szerotoninreceptor-agonisták, tumornekrózis-faktor-alfa-blokkolók, a komplement alternatív útjának specifikus gátlója, kurkumin és a doxiciklin. Az endothel működésének helyreállítása stabilizálja az állapotot idült érbetegségek, így időskori maculadegeneráció esetében is. Az emberi érrendszer egylényegűségét is tekintetbe véve a megelőzésre a felsorolt gyógyszereket azoknak a betegeknek kell adni, (1) akiknek nincs maculadegenerációja, de fennállnak az időskori maculadegeneráció endothelműködés-zavart kiváltó kockázati tényezői és 50 évesnél idősebbek, (2) akiknél egyoldali időskori maculadegenerációt állapítottak meg, a másik szem károsodásának a megelőzésére, valamint (3) kétoldali időskori maculadegenerációban szenvedőknek a romlás kivédésére és az esetleges javulás reményében. Mindezekhez randomizált prospektív klinikai vizsgálatok szükségesek. Orv. Hetil., 2015, 156(46), 1847–1858.

  • 1

    Fischer, T.: The age-related macular degeneration (AMD) may be vascular disease, part of vasculopathy, respectively. Novel considerations on AMD arising from the newest pathophysiological, clinical and clinical-pharmacological observations. (Preliminary communication.) J. Neurosci. Behav. Health, 2012, 4(5), 42–49.

  • 2

    Cheung, C. M., Wong, T. Y.: Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J. Intern. Med., 2014, 276(2), 140–153.

  • 3

    Münzel, T., Gori, T.: Nebivolol: the somewhat-different beta-adrenergic receptor blocker. J. Am. Coll. Cardiol., 2009, 54(16), 1491–1499.

  • 4

    Ishida, S.: Lifestyle-related diseases and anti-aging ophthalmology: suppression of retinal and choroidal pathologies by inhibiting renin-angiotensin system and inflammation. Nihon Ganka Gakkai Zasshi, 2009, 113(3), 403–422. [Japanese]

  • 5

    Heagerty, A. M.: Effect of AT1-receptor blockade on cardiovascular structure and function. Eur. Heart J., 2004, 6(Suppl. H), H17–H21.

  • 6

    Jackson, E. K.: Renin and angiotensin: drugs affecting renal and cardiovascular function. In: Brunton, L. L., Lazo, J. S., Parker, K. L. (eds.): Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill, New York, 2006.

  • 7

    Koh, K. K., Quon, M. J., Han, S. H., et al.: Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs. Int. J. Cardiol., 2010, 140(1), 73–81.

  • 8

    Lonn, E., Gerstein, H. C., Smieja, M., et al.: Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies. Eur. Heart J., 2003, 5(Suppl. A), A43–A48.

  • 9

    Soehnlein, O., Schmeisser, A., Cicha, I.: ACE inhibition lowers angiotensin-II-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression. J. Vasc. Res., 2005, 42(5), 399–407.

  • 10

    López-Sendón, J., Swedberg, K., McMurray, J., et al., The Task Force on ACE-inhibitors of the European Society of Cardiology: Expert consensus document on angiotensin converting enzyme inhibitors in vascular disease. Eur. Heart J., 2004, 25(16), 1454–1470.

  • 11

    Wassmann, S., Laufs, N., Bäuner, A. T., et al.: Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol. Pharmacol., 2001, 59(3), 646–654.

  • 12

    Wassmann, S., Nickenig, G.: The role of AT1-receptor in the cardiovascular continuum. Eur. Heart J., 2004, 6(Suppl. H), H3–H9.

  • 13

    Landmesser, U., Harrison, D. G.: Oxidant stress as a marker for cardiovascular events. Ox marks the spot. Circulation, 2001, 104(22), 2638–2640.

  • 14

    Montero, J. A., Ruiz-Moreno, J. M., Sanchis-Merino, E., et al.: Systemic beta-blockers may reduce the need for repeated intravitreal injections in patients with wet age-related macular degeneration treated by bevacizumab. Retina, 2013, 33(3), 508–512.

  • 15

    Erusalimsky, J. D.: Vascular endothelial senescence: from mechanisms to pathophysiology. J. Appl. Physiol., 2009, 106(1), 326–332.

  • 16

    Coleman, H. R., Chan, C. C., Ferris, F. L. 3rd, et al.: Age-related macular degeneration. Lancet, 2008, 372(9652), 1835–1845.

  • 17

    Pershadsingh, H. A., Moore, D. M.: PPAR gamma agonists: Potential as therapeutics for neovascular retinopathies. PPAR Res., 2008, 2008, 164273.

  • 18

    Steinmetz, M., Brouwers, C., Nickenig, G., et al.: Synergistic effects of telmisartan and simvastatin on endothelial progenitor cells. J. Cell. Mol. Med., 2010, 14(6B), 1645–1656.

  • 19

    Ceriello, A.: New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care, 2003, 26(5), 1589–1596.

  • 20

    Molavi, B., Metha, J. L.: Oxidative stress in cardiovascular disease: molecular basis of its deleterious effects, its detection, and therapeutic considerations. Curr. Opin. Cardiol., 2004, 19(5), 488–493.

  • 21

    Asselbergs, F. W., van der Harst, P., Jessurun, G. A., et al.: Clinical impact of vasomotor assessment and role of ACE-inhibitors and statins. Vascul. Pharmacol., 2005, 42(3), 125–140.

  • 22

    McMurray, J., Solomon, S., Pieper, K., et al.: The effect of valsartan, captopril or both on arteriosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J. Am. Coll. Cardiol., 2006, 47(4), 726–733.

  • 23

    Ferrari, R., Guardigli, G., Ceconi, C.: Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium. Cardiovasc. Drugs Ther., 2010, 24(4), 331–339.

  • 24

    Wilkinson-Berka, J. L., Miller, A. G., Fletcher, E. L.: Prorenin and the (pro)renin receptor: do they have a pathogenic role in the retina? Front. Biosci. (Elite Ed.), 2010, 2, 1054–1064.

  • 25

    Lu, X., Danser, A. H., Meima, M. E.: HRP and prorenin: focus on the (pro)renin receptor and vacuolar H+-ATPase. Front. Biosci. (Schol. Ed.) 2011, 3, 1205–1215.

  • 26

    Borghi, C., Morbini, M., Cicero, A. F.: Combination therapy in the extended cardiovascular continuum: a focus on perindopril and amlodipine. J. Cardiovasc. Med. (Hagerstown), 2015, 16(5), 390–399.

  • 27

    Wight, S. A., O’Prey, F. M., McHenry, M. T., et al.: A randomized interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus arythematosus. Ann. Reum. Dis., 2008, 67(6), 841–848.

  • 28

    Hasler, P. W., Flammer, J.: Predictive, preventive and personalised medicine for age-related macular degeneration. EPMA J., 2010, 1(2), 245–251.

  • 29

    Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol., 2001, 119(10), 1417–1436.

  • 30

    Almutti, K., Rimawi, R., Spevack, D., et al.: Effects of statins beyond lipid lowering: potential for clinical benefits. Int. J. Cardiol., 2006, 109(1), 7–15.

  • 31

    Hall, N. F., Gale, C. R., Syddall, H., et al.: Risk of macular degeneration in users of statins: cross-sectional study. BMJ, 2001, 323(7309), 375–376.

  • 32

    Tomita, M., Yamada, H., Adachi, Y., et al.: Choroidal neovascularization is provided by bone marrow cells. Stem Cells, 2004, 22(1), 21–26.

  • 33

    Niessen, S. E., Tuzcu, E. M., Schoenhagen, P., et al.: Statin-therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N. Engl. J. Med., 2005, 352(1), 29–38.

  • 34

    Ray, K. K., Cannon, C. P.: The potential relevance of the multiple lipid-indipendent (pleiotropic) effects of the statins in the management of acute coronary syndromes. J. Am. Coll. Cardiol., 2005, 46(8), 1425–1433.

  • 35

    Wydlanski, M. E., Gokce, N., Keaney, J. F. Jr., et al.: The clinical implications of endothelial dysfunction. J. Am. Coll. Cardiol., 2003, 42(7), 1149–1160.

  • 36

    Honjo, M., Tanihara, H., Nishijima, K.: Statins inhibits leukocyte-endothelial interaction and prevents neuronal death induced by ischemia-reperfusion injury in the rat retina. Arch. Ophthalmol., 2002, 120(12), 1707–1713.

  • 37

    Palinski, W., Tsimikas, S.: Immunomodulatory effects of statins: mechanisms and potential impact on arteriosclerosis. J. Am. Soc. Nephrol., 2002, 13(6), 1673–1681.

  • 38

    McGwin, G. Jr., Owsley, C., Curcio, C. A., et al.: The association between statin use and age related maculopathy. Br. J. Ophthalmol., 2003, 87(9), 1121–1125.

  • 39

    Ajamieh, H., Farrell, G. C., McCuskey, R. S., et al.: Acute atorvastatin is hepatoprotective against ischaemia-reperfusion injury in mice by modulating eNOS and microparticle formation. Liver Int., 2015, 35(9), 2174–2186.

  • 40

    Song, Q., Wang, L., Zhu, J., et al.: Effect of simvastatin on inducing endothelial progenitor cells homing and promoting bone defect repair. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2010, 24(9), 1103–1106.

  • 41

    Ota, H., Eto, H., Kano, M. R., et al.: Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler. Thromb. Vasc. Biol., 2010, 30(11), 2205–2211.

  • 42

    Owens, A. P. 3rd, Mackman, N.: The antithrombotic effects of statins. Annu. Rev. Med., 2014, 65, 433–445.

  • 43

    Fassett, R. G., Robertson, I. K., Ball, M. J., et al.: Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease. Clin. Nephrol., 2014, 81(2), 75–85.

  • 44

    Kubota, S., Kurihara, T., Ebinuma, M., et al.: Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation. Am. J. Pathol., 2010, 177(4), 1725–1731.

  • 45

    Gaynes, B. I.: Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among age-related macular degeneration patients. Am. J. Ophthalmol., 2004, 138(6), 1089.

  • 46

    Wilson, H. L., Schwartz, D. M., Bhatt, H. R., et al.: Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration. Am. J. Ophthalmol., 2004, 137(4), 615–624.

  • 47

    Marti, C. N., Gheorghiade, M., Kalogeropoulos, A. P., et al.: Endothelial dysfunction, arterial stiffness, and heart failure. J. Am. Coll. Cardiol., 2012, 60(16), 1455–1469.

  • 48

    Morgan, C. L., Owens, D. R., Aubonnet, P., et al.: Primary prevention of diabetic retinopathy with fibrates: a retrospective, matched cohort study. BMJ Open, 2013, 3(12), e004025.

  • 49

    Wu, R., Lamontagne, D., de Champlain, J.: Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation, 2002, 105(3), 387–392.

  • 50

    Wu, R., Laplante, M., de Champlain, J.: Prevention of angiotensin-II-induced hypertension and cardiovascular hypertrophy and oxidative stress by acetylsalicylic acid in rats. J. Hypertens., 2004, 22(4), 793–801.

  • 51

    Yoon, J. W., Cho, B. J., Park, H. S., et al.: Differential effects of trimetazidine on vascular smooth muscle cell and endothelial cell in response to carotid artery balloon injury in diabetic rats. Int. J. Cardiol., 2013, 167(1), 126–133.

  • 52

    Coyas, A.: The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial. Ann. Otolaryngol. Chir. Cervicofac., 1990, 107(Suppl. 1), 82–87.

  • 53

    Dézsi, C. A.: Trimetazidine in practice: Review of the clinical and experimental evidence. Am. J. Ther., 2014 Jan 7. [Epub ahead of print]

  • 54

    Belardinelli, R., Solenghi, M., Volpe, L.: Trimetazidine improves endothelial dysfunction in chronic heart failure: an antioxidant effect. Eur. Heart J., 2007, 28(9), 1102–1108.

  • 55

    Vitale, C., Wajngaten, M., Sposato, B.: Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease. Eur. Heart J., 2004, 25(20), 1814–1821.

  • 56

    Kaszuba-Bartkowiak, K., Nowak, M. S., Jurowsky, P., et al.: The role of trimetazidine in the protection of the retina. Arch. Med. Sci., 2007, 3, S65–S66.

  • 57

    Mahfoudh-Boussaid, A., Hadj Ayed Tka, K., Zaouali, M. A., et al.: Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in an in vivo rat model of renal ischemia-reperfusion. Ren. Fail., 2014, 36(9), 1436–1442.

  • 58

    Demir, T., Torgut, B., Ozercan, I., et al.: Trimetazidine for prevention of induced ischemia and reperfusion of guinea pig retina. Clin. Ophthalmol., 2010, 4, 21–26.

  • 59

    Wu, T. C., Chen, Y. H., Leu, H. B., et al.: Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Free Radic. Biol. Med., 2007, 43(11), 1508–1522.

  • 60

    Thuillez, C.: Endothelial dysfunction: role of vasodilating betablockers in hypertension and chronic heart failure. Ann. Cardiol. Angeiol. (Paris), 2010, 59(2), 86–92.

  • 61

    Sorrentino, S. A., Doerries, C., Manes, C.: Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional β1-blockade. J. Am. Coll. Cardiol., 2011, 57(5), 601–611.

  • 62

    Conti, V., Russomanno, G., Corbi, G., et al.: Adrenoreceptors and nitric oxide in the cardiovascular system. Front. Physiol., 2013, 4, 321. doi: 10.3389/fphys.2013.00321

  • 63

    Hwang, J., Kleinheinz, D. J., Rupnow, H. L., et al.: The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice. Vascul. Pharmacol., 2007, 46(6), 456–462.

  • 64

    Cockcroft, J.: A review of the safety and efficacy of nebivolol in the mildly hypertensive patient. Vasc. Health Risk Manag., 2007, 3(6), 909–917.

  • 65

    Herzlich, A. A., Tuo, J., Chan, C. C.: Peroxisome proliferator-activated receptor and age-related macular degeneration. PPAR Res., 2008, 2008, 389507.

  • 66

    Shab-Bidar, S., Neyestani, T. R., Djazayery, A., et al.: Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab. Res. Rev., 2012, 28(5), 424–430.

  • 67

    Rastmanesh, R.: Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity. Med. Hypotheses, 2011, 76(1), 79–85.

  • 68

    Rosen, R., Hu, D. N., Perez, V., et al.: Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Mol. Vis., 2009, 15, 1673–1679.

  • 69

    Zieman, S. J., Melenovsky, V., Clattenburg, L., et al.: Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J. Hypertens., 2007, 25(3), 577–583.

  • 70

    Mouchiroud, L., Molin, L., Dalliére, N., et al.: Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging. Biofactors, 2010, 36(5), 377–382.

  • 71

    Ho, Y. S., Poon, D. C., Chan, T. F., et al.: From small to big molecules: how do we prevent and delay the progression of age-related neurodegeneration? Curr. Pharm. Des., 2012, 18(1), 15–26.

  • 72

    Sharma, A., Bernatchez, P. N., de Haan, J. B.: Targeting endothelial dysfunction in vascular complications associated with diabetes. Int. J. Vasc. Med., 2012, 2012, 750126.

  • 73

    Jablecka, A., Bogdanski, P., Balcer, N., et al.: The effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities. Eur. Rev. Med. Pharmacol. Sci., 2012, 16(3), 342–350.

  • 74

    Gao, L., Mao, Q., Cao, J., et al.: Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials. Atherosclerosis, 2012, 221(2), 311–316.

  • 75

    Nakajima, Y., Inokuchi, Y., Nishi, M., et al.: Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo. Brain Res., 2008, 1226, 226–233.

  • 76

    Blasi, M. A., Bovina, C., Carella, G., et al.: Does coenzyme Q10 play a role in opposing oxidative stress in patients with age-related macular degeneration? Ophthalmologica, 2001, 215(1), 51–54.

  • 77

    Thampi, P., Rao, H. V., Mitter, S. K., et al.: The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium. PLoS ONE, 2012, 7(4), e34468.

  • 78

    Mirshaki, A., Hoehn, R., Lorenz, K., et al.: Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts. J. Ophthalmic Vis. Res., 2012, 7(1), 39–44.

  • 79

    Rohrer, B., Long, Q., Coughlin, B., et al.: A targeted inhibitor of the alternative complement pathway reduces angiogenesis in a mouse model of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci., 2009, 50(7), 3056–3064.

  • 80

    Scott, I. U., Jackson, G. R., Quillen, D. A., et al.: Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol., 2014, 132(5), 535–543.

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Sep 2020 110 0 0
Oct 2020 64 1 1
Nov 2020 63 9 2
Dec 2020 19 0 0
Jan 2021 33 0 0
Feb 2021 19 0 0
Mar 2021 7 0 0