Interphotoreceptor Retinoid Binding Protein; Myths and Mysteries

Although it is the major soluble protein component of the extracellular matrix bathing the photoreceptors, little is known about the structure and function of interphotoreceptor retinoid-binding protein (IRBP). The critical anatomic compartment it occupies cannot be overemphasized as through the involution of the optic vesicle, the retinal pigmented epithelium (RPE) comes in contact with the neural retina.1 The zonula occludens and adherens of the RPE and external limiting membrane respectively restrict the interphotoreceptor matrix (IPM) to the “subretinal space”. Given its presence at this interface and early expression patterns, IRBP could have a function in retinal development,2,3 and recent studies point to a role in eye growth4. Early studies assumed that IRBP does not interact with components of the IPM or retina, as it is easily extracted from detached retinas by only gentle saline wash. This notion, recently revisited experimentally,5 has shown not to be completely true as saline wash leaves behind IRBP tightly bound to specific regions, particularly a domain surrounding the cone outer segments, presumably the cone matrix sheath (Fig. 1). An important question, which has received insufficient attention, is what are the binding partners that IRBP interacts with in the IPM and/or on the cell surface?