Abstract

THE AGE-RELATED MACULAR DEGENERATION AS A VASCULAR DISEASE: CONTRIBUTIONS TO ITS PATHOGENESIS.

Dr. Tamás Fischer, M. D.

ABSTRACT

The endothelial system assures unhindered functioning and stability of the internal milieu maintaining vascular health and protecting against vascular injury, noxa by excreting various substances: vasodilators and vasoconstrictors, growth factors and their inhibitors, proinflammatory and antiinflammatory agents, pro-thrombotic and fibrinolytic factors, and by keeping them in a strict equilibrium: endothelial dysfunction is the change of these properties, what is inappropriate with regard to the preservation of organ function. In the genesis and later development of age-related macular degeneration (AMD), endothelial dysfunction (ED) has a crucial role. AMD-risk factors, correlate with, and often are identical wih the risk factors (RFs) of cardiovascular diseases (CVDs), These risk factors lead to chronic vascular injury based on the same mechanism of action, by inducing oxidative stress (OS): harms (noxa, RFs) → oxidative stress (OS) → endothelial activation (EA), endothelial dysfunction (ED), respectively → vacular injury, vascular disease. Disordered function of endothelium (ED) of vessels supplying the affected ocular structures with blood 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 (host defense response) i.e. increased ROS formation → oxidative stress → endothelial activation/dysfunction → aftermath of EA/ED may develop, and in consequence of this chronic vascular damage, pathological consecutive changes ending in AMD, ultimately, may develop: all this goes to show that AMD may be a local manifestation of systemic (vascular) disease. 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: primary abnormalities in ocular perfusion worsen with age, secondarily causing dysfunction of the retinal pigment epithelial cells, predisposing eyes to AMD. Theese changes together with individual’s (environmental) risk factors set the stage for the development of AMD. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration (AMD) may be a vascular disease, part of systemic vasculopathy(!): disordered function of the endothelium of vessels supplying the affected ocular structures with blood plays a major role in the genesis and development of age-related macular degeneration. This recognition should have therapeutic implications because restoration of endothelial dysfunction can re-stabilize the condition of chronic vascular disease including age-related macular degeneration as well: recovering of endothelial dysfunction by non-pharmacological and/or pharmacological interventions may prevent the development and improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration as well.

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