A szem struktúráit vérrel ellátó érendothelium működészavarának kulcsfontosságú a szerepe az időskori maculadegeneráció létrejöttében, és indirekt bizonyítékok arra utalnak, hogy az időskori maculadegeneráció érbetegség, végső soron az egész érrendszer megbetegedésének a része. Az ártalmak, a rizikófaktorok oxidatív stresszhez vezetnek, ami aktiválja az endothelt, és szövetkárosodás alakul ki. Az erek, így a szem érhártyájában, a chorioideában lévő erek falát is számos ismétlődő és/vagy elhúzódó inger éri, amelyek mechanikai, fi zikai, kémiai, mikrobiológiai, immunológiai, illetve genetikai eredetűek lehetnek. Bármilyen hosszan tartó/ismétlődő ártalom, amely működésbe hozza a védekezés láncreakcióját, gyulladást vált ki. Az ártalmas behatás eliminálásának sikertelensége endothelműködés-zavart, ér/szö-vet károsodást, időskori maculadegenerációt eredményez(het). Mindezek a tények arra utalnak, hogy az időskori maculadegeneráció érbetegség, az egész érrendszer megbetegedésének a része. Ami a kockázati tényezők jelenlé tében kialakuló endotheldiszfunkció és következményes időskori maculadegeneráció kiküszöbölésének, megelőzésének, illetve megszüntetésének stratégiáját illeti, számos jótékony nem gyógyszeres és farmakológiai intervenció áll rendelkezés-re: joggal várható, hogy az endotheldiszfunkció helyreállítása megakadályozza az érbántalom és így az időskori maculadegeneráció kialakulását vagy csökkenti a már kialakult elváltozást. Orv. Hetil., 2015, 156(9), 358-365.Kulcsszavak: időskori maculadegeneráció, endotheldiszfunkció, oxidatív stressz, kockázati tényező, prevenció, preventív terápiaThe age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesisThe wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in infl ammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic infl ammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general infl ammatory response, in the form of complement system activation, similar to that observed in de...

In the genesis and later development of age-related macular degeneration (AMD), endothelial dysfunction (ED) has a crucial role. AMD-risk factors, which play a decisive role in AMD, are in a close connection, correlate with, and often are identical wih the risk factors (RFs) of cardiovascular diseases (CVDs), so that it can reasonably be presumed that the two conditions have a similar pathogenesis. These risk factors, which seem essentially different, lead to chronic vascular injury based on the same mechanism of action: by inducing oxidative stress (OS). ED itself is a consequential-consecutive phenomenon (OS→ED!), and is a clinico-pathophysiologically important connecting link between harm(s)/noxa and vascular injury (harm [noxa] → oxidative stress (OS) → endothelial activation (EA), endothelial dysfunction (ED), respectively → vacular injury, vascular disease). Disordered function of endothelium in the vessels supplying the affected ocular structures with blood (ED) have a key role in the genesis and development of age-related macular degeneration. Changes in blood vessels including those in choroids may be triggered by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic influences/impacts/noxa (in fact, the risk factors!), against which protracted response 1 **) (increased ROS formation → oxidative stress → endothelial activation/dysfunction → aftermath of EA/ED) may develop, and in consequence of this, (chronic) vascular damage (functional and then structural alteration [remodelling] of the blood vessel), pathological consecutive changes ending in AMD, ultimately, may develop (choriocapillaris degenerates in exudative AMD, choriocapillaris degeneration precedes retinal pigment epithelial atrophy in wet AMD). All this goes to show that AMD may be a local manifestation of systemic (vascular) disease, undoubtedly. AMD is the disease of the aging body. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD. Advancing age is a privotal and independent risk factor for vascular disease as can be understood from the fact that aging individuals often demonstrate dysfunctional blood vessel repair after vascular injury and aging per se, in the absence of other risk factors is associated with oxidative/nitrosative stress and inflammatory changes in the phenotype of blood vessels (primary abnormalities in ocular perfusion worsen with age, secondarily causing dysfunction of the retinal pigment epithelial cells, predisposing eyes to AMD), these changes together with individual's (environmental) risk factors set the stage for the development Fischer 43 of AMD. Regarding therapy/preventive treatment/prevention of AMD: (I) Non-medicinal (preventive) treatment such as lifestyle modifications of AMD patients (modifying lifestyles behavours of diet, smoking and physical activity) is of indispensable importance; they influence strongly and very beneficially the established vascular risk factors and also advantageously affect ...

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into consideration all possible side effects--ACE-inhibitor and/or AR blocker and statin and aspirin treatment, and trimetazidine as adjuvant medicine, and third generation beta adrenergic receptor blockers: 1. those without macular degeneration but being above the age of 50 and having risk factors inducing endothelial dysfunction; 2. those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3. those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory and important to eliminate AMD risk factors (cardiovascular risk factors also) inducing oxidative stress with consecutive endothelial dysfunction.

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into consideration all possible side effects--ACE-inhibitor and/or AR blocker and statin and aspirin treatment, and trimetazidine as adjuvant medicine 1. those without maculopathy but being above the age of 50 and having risk factors inducing endothelial dysfunction; 2. those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3. those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory to eliminate AMD risk factors inducing oxidative stress with consecutive endothelial dysfunction.

No abstract