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Abstract

THE AGE-RELATED MACULAR DEGENERATION AS A VASCULAR DISEASE: CONTRIBUTIONS TO THE NON- PHARMACOLOGICAL INTERVENTIONS AND PHARMACOLOGICAL THERAPY ARISING FROM ITS PATHOGENESIS.

Dr. Tamas Fischer M.D.

ABSTRACT

It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompaniedby a general inflammatory response. The vascular wall including those in chorioids may be activated by severalrepeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age- related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including agerelated macular degeneration, as well. Restoration of endothelial dysfunction by non pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Nonpharmacological interventions which may have beneficial effect in endothelial dysfunction include(1) smoking cessation;(2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins, (d) management of dietary glycemic index, (e) caloric restriction, and (5) of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.- It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Pharmacological interventions (medicines) including (1) inhibitors of the renin-angiotensin system ([a] converting enzyme inhibitors, [b] angiotensin-receptor blockers and [c] renin inhibitors), (2) statins, (3) acetylsalicylic acid, (4) trimetazidin, (5) third generation betablockers, (6) peroxisome proliferator-activated receptor gamma agonists, (7) folate, (8) vitamin D, (9) melatonin, (10) advanced glycation end-product (11) crosslink breaker alagebrium, (12) endothelin-receptor antagonist bosentan, (13) coenzyme Q10; (14) “causal” antioxidant vitamins, (a) FP015 metalloporphyrin compound (b) INO-1001; (15) N-acetyl-cysteine, (16) resveratrol, (17) L-arginine, (18) serotonin receptor agonists [5- HT(1A) receptor agonists] 8-Oh DPAT, (19) tumor necrosis factor-alpha blockers, (20) curcumin and (21) doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

Keywords: age-related macular degeneration, endothelial dysfunction, oxidative stress, risk factors, primary and secondary prevention, non-pharmacological intervention, pharmacological intervention, lifestyle modifications.


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