Age-related maculopathy (ARM) is a severe threat to the visual ability of people over 65 years of age. In the late stages of ARM, called age-related macular degeneration (AMD), photoreceptor cells gradually disappear. New vessels growing beneath the retina may complicateb the disease; this is called âwetâ or neovascular AMD. Knowledge about causes and pathogenesis of this eye disease could lead to therapies, and probably even more important, to strategies that prevent the disease from occurring. The purpose of this thesis was to study several of many molecular changes that occur during the development of ARM.
Growth factors play a role in choroidal neovascularization. With advancing age, the thickness of the retina decreases. Little is known about the way cells disappear during this process. Apoptosis was studied in the macula of rhesus monkeys of different ages. The findings indicate that apoptosis in the primate macula occurs at all ages at similar rate, possibly increasing in the oldest age group, and may account for the decreasing thickness of the primate macula with age. It appears to be unlikely that Fas-ligand (FasL) expressed on retinal pigment epithelium controls the extension of choroidal neovascularization. Several growth factors could be involved in the pathogenesis of neovascular AMD. The results may point towards a role of the Insulinlike Growth Factors in the pathogenesis of neovascular AMD.
Somatostatin reduces newly formed vessels by inhibiting the growth hormone/insulin-like growth factor axis and also has a direct anti-proliferative effect on various cell types involved in angiogenesis. It is demonstrated that most early-formed choroidal neovascularization in eyes of patients with AMD express sst2A, which is a receptor for somatostatin. The sst2A receptor binds potential anti-angiogenic somatostatin-analogues like octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of neovascular AMD
