Expression of integrins on human choroidal neovascular membranes

Most of the focus in choroidal and retinal angiogenesis centers on the regulation of endothelial function by soluble factors. Less well-understood, but nevertheless significant, is the regulation of endothelial cell function by its insoluble microenvironment, the extracellular matrix (ECM). Endothelial interaction with the ECM occurs primarily through cell surface receptors belonging to the integrin family that relay information from the ECM to the intracellular signaling machinery. The integrin family is composed of 24 heterodimeric type I transmembrane cell surface receptors containing an alpha and a beta subunit. To date, there are known to be 18 alpha and eight beta subunits [1]. Alpha subunits are designated 1–11, iib, v, D, E, L, M, and X. Beta subunits have designations of 1–8. The heterodimeric receptor is designated through identification of the corresponding alpha and beta subunits, e.g., αiibβ3 designates the platelet integrin. The ECM specificity of individual integrin family members covers a broad spectrum of selectivity as exemplified by the restricted specificity of the α5β1 integrin for only fibronectin and the promiscuous binding of the αvβ3 to a diverse set of ECM [2]. Even with this disparity in matrix selectivity, integrin family members can be categorized based on the subset of matrices recognized and cell type expression patterns. The four categories consist of integrins that preferentially bind collagen, laminin, or ECM containing an arg-gly-asp (RGD) tripeptide motif and integrins which are primarily leukocytespecific receptors [1, 2]. The ability of a number of integrins to recognize the same primary matrix implies that there is potential overlap among family members. While there clearly can be some degree of functional compensation, as seen in the ability of the αvβ3 integrin to supplement fibronectin matrix assembly in the absence of α5β1 integrin [3], this functional compensation is incomplete, implying that each family member is likely to have a crucial functional role within a given biological process. The functional activity of integrin family members can be typically viewed as having a permissive role in providing adhesive function; however, in some cases, this role may be regulatory rather than permissive in nature, as in the case of the αvβ3 integrin, which is believed to modulate neovascular response [4]. Furthermore, the functional activity may also depend on the presence of other integrin family members, which may suppress function via a mechanism of transmodulation known as transdominance [5, 6]. It is clear that in order to gain a better understanding of how cell adhesion, and especially integrins, regulate a biological process, it is essential to j ocul biol dis inform (2009) 2:12–19 DOI 10.1007/s12177-009-9015-9