Dis­ease patho­logy

Age-Re­lated Mac­ula De­gen­er­a­tion (AMD) is a ma­jor cause of blind­ness in eld­erly people in in­dus­tri­al­ised coun­tries. You can dis­tin­guish the at­roph­ic (“dry”) and the ex­ud­at­ive (“wet”) form, which is the more dev­ast­at­ing one. Both are pro­moted by vari­ous en­vi­ron­men­tal risk factors as well as ge­net­ic factors. The ex­ud­at­ive form of AMD is char­ac­terised by the in­growth of ves­sels in­to the cent­ral part of the reti­na that nor­mally is free of blood ves­sels (“choroid­al neovas­cu­lar­isa­tion, CNV”). This CNV is triggered by an im­bal­ance of an­giogen­ic (ves­sel growth pro­mot­ing) and anti-an­giogen­ic (ves­sel growth in­hib­it­ing) factors in fa­vour of ves­sel growth. Most prom­in­ent mo­lecules are the an­giogen­ic vas­cu­lar en­dotheli­al growth factor (VEGF) and the anti-an­giogen­ic pro­tein pig­ment ep­ithe­li­um-de­rived factor (PEDF). All these dev­ast­at­ing pro­cesses are fo­cused on the mac­ula, the place for cent­ral and sharp vis­ion in the hu­man reti­na.

The patho­logy of AMD prob­ably starts with an impair­ment of the RPE (reti­nal pig­ment ep­ithe­li­um) cell lay­er. The reas­ons for this loss of func­tion are not com­pletely un­der­stood. In­flam­ma­tion, cel­lu­lar stress and ge­net­ic pre­dis­pos­i­tion are pos­sible causes for the de­gen­er­a­tion that, un­treated, leads to blind­ness. The RPE cells are no longer able to pre­serve a func­tion­al reti­na by sus­tain­ing the visu­al cells, sup­port­ing them with es­sen­tial nu­tri­ents, re­gen­er­at­ing the light-sen­si­tive mo­lecule op­sin and dis­pos­ing of waste products.

In dry AMD, waste products ac­cu­mu­late in and around the RPE cells form­ing so-called drusen that dam­age the RPE cells, which fi­nally die. Con­sequently, the RPE cells can no longer pre­serve the visu­al cells, which will de­gen­er­ate next. In ex­ud­at­ive AMD, Bruch’s mem­brane, a bar­ri­er of the out­er reti­na, will be­come per­meable and ves­sels from the will pen­et­rate the reti­na. Ad­di­tion­ally, a per­turbed cel­lu­lar meta­bol­ism leads to an im­bal­ance of an­giogen­ic and anti-an­giogen­ic factors, pro­mot­ing ves­sel growth in the reti­na, which un­treated leads to reti­nal de­gen­er­a­tion and blind­ness.