The role of Eph receptors in lens function and disease

Abstract

Cataract is the single largest contributor to blindness in the world, with the disease having a strong genetic component. In recent years the Eph family of receptor tyrosine kinases has been identified as a key regulator in lens clarity. In this review we discuss the roles of the Eph receptors in lens biology and cataract development.

Figure 1

A cross-sectional view of the mature lens. The core of the lens consists of irregularly-shaped primary lens fiber cells formed during the early stages of lens development. After the initial development of primary fiber cells, secondary lens fiber cells form continuously from this core and are arranged in regular hexagonal structures. The anterior face of the lens contains a monolayer of lens epithelial cells (LE) that continually divide and differentiate into secondary lens fiber cells. The entire structure is encapsulated by a lens capsule (LC). * denotes gap junction complexes along the long edges of secondary fiber cells.

Figure 2

Human EphA2 cataract mutations. A, Structure of wild-type EphA2. BD, ephrin ligand binding domain; FN, fibronectin repeats; Kin, kinase domain; SAM, sterile alpha motif; PDZ, PDZ domain. B, EphA2 SAM Domain cataract mutants. C, EphA2 kinase domain cataract mutants. Arrows denote relative location of point mutations in indicated mutations. Black boxes denote novel amino acid changes.

Figure 3

Expression of ephrin-A5 and EphA2 during ocular development. A–C, Ephrin-A5 expression at E12 (A), E14 (B), and E17 (C) is observed in the lens epithelium, lens fiber layer around the bow region, cornea, and the retina. Expression within the retinal region is graded with higher expression towards the nasal retina. Ephrin-A5 levels within the developing eye are reduced at later stages. D–F, EphA2 expression at E12 (D), E14 (E), and E17 (F) is observed in the lens epithelium, fiber cell layers, and parts of the retina during ocular development (data unpublished). Within the lens, EphA2 is observed in several of the same regions as ephrin-A5 has been found to be expressed (data unpublished). LE, lens epithelium; LF, lens fiber cells layer; Re, retina; Co, cornea; N, nasal retina; T, temporal retina.