Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications

Abstract

Choroidal neovascularization (CNV) is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.

Figure 1

Fluorescein angiography of a classic choroidal neovascularization. (a) Early and (b) late angiograms: the lesion is characterized by a well demarcated area of early fluorescence with a progressive leakage of the dye to the subretinal space leading to blurring of the borders in the late phase of the exam.

Figure 2

Fluorescein angiography of a predominantly classic choroidal neovascularization. (a) Early and (b) late angiograms: the lesion has a mixture of angiographic features of the classic and occult type, with the classic component making up more than 50% of the entire neovascular complex.

Figure 3

Fluorescein angiography of a minimally classic choroidal neovascularization. (a) Early and (b) late angiograms: the lesion has a mixture of the angiographic features of the classic and occult type, with the classic component making up less than 50% of the entire neovascular complex.

Figure 4

Fluorescein angiography of an occult choroidal neovascularization. (a) Early and (b) late angiograms: the lesion appears within 1-2 minutes from the start of the exams and persists during the late phase; it is characterized by areas of irregular elevation of the retinal pigment epithelium that present stippled hyperfluorescence.