A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations

Abstract

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.

Statins: What is Beyond Hyperlipidemia?

“…Keeping in mind the uniformity of the vascular system physiologically and pathophysiologically, and that it plays a key role in age-related macular degeneration (AMD), endothelial dysfunction should be treated [5,6]. Age-related macular degeneration is a progressive late onset disease affecting central vision, representing the leading cause of irreversible blindness among older adults, affecting one in three people aged 75 or older, and with the aging population the problem is increasing [7,8].…”

Therapeutic Potential of Statins in Age-related Macular Degeneration

“…Given the fact that the vascular system is uniform and physiologically and pathophysiologically consubstantial and in terms of therapy, it plays a key role in ARMD, endothelial dysfunction should be treated (Fisher, 2008;2009). Self reported use of cholesterol lowering medications was associated with a four-fold decreased risk of ARMD progression in those who had ARMD at baseline (McCarty et al, 2001); however, because of small sample size, this finding was not statistically significant.…”