The interphotoreceptor matrix, a space in sight

Abstract

The interphotoreceptor matrix (IPM) has in recent years been receiving much attention due to its delicate localization between the photoreceptors and the retinal pigment epithelium (RPE). The IPM is a resilient, structure forming and hydrophilic matrix composed of large glycoproteins and proteoglycans, which occupies the subretinal space between the photoreceptors. The IPM is most likely assembled with components synthesized by all the surrounding cell types: the photoreceptor cells, the RPE cells, and the Müller cells. It has been implied to be involved in the development and maintenance of photoreceptors, and as a major factor in retinal adhesion. Therefore, it has been thoroughly studied also in several models of photoreceptor degeneration. Comparative studies have revealed some remarkably consistent features between different species, such as the presence of the rod and cone specific matrix domains. Studies made in the IPM of several species have measured large fluctuations in ion concentrations as a result of changes in illumination. In some species, these ionic fluctuations coincide with the intriguing dynamic redistributions of IPM constituents that can be visualized with histochemical techniques. It can be hypothesized that because of the intensive biochemical activity and the frequent changes in metabolic states of rods and cones the IPM may act as a kind of "buffer." These studies have brought a new extracellular aspect to photoreceptor studies and a new perspective to photoreceptor-RPE research.

Evolution of the visual cycle: the role of retinoid-binding proteins

“…To mediate the varied critical interactions between the RPE and neural retina, the two layers are separated by a fascinating extracellular matrix known at the IPM (reviewed by Bridges & Adler 1985, Hageman & Johnson 1991, Mieziewska 1996, Hollyfield 1999 (Fig. 1).…”

Combined Rod and Cone Transduction by Adeno-Associated Virus 2/8

“…PR transduction appears more challenging than RPE transduction, likely because of the organization of PRs into tight rows (Clarke et al, 2000) and to the presence of both interphotoreceptor matrix and outer limiting membrane that may restrict access to PRs upon subretinal injections (Mieziewska, 1996;Omri et al, 2010). Among the naturally occurring serotypes previously tested in the retina, AAV2/5, AAV2/8, and AAV2/9 have been shown to be the most efficient for transduction of the outer nuclear layer (ONL) cells in mice (Allocca et al, 2007;Lebherz et al, 2008), pigs (Mussolino et al, 2011), and nonhuman primates (NHP) (Mancuso et al, 2009;Vandenberghe et al, 2011Vandenberghe et al, , 2013.…”

Gene Therapy of Inherited Retinopathies: A Long and Successful Road from Viral Vectors to Patients

“…However, the transduction of mature PRs remains the fundamental limitation of LVs and Ads as vectors for the therapy of IRs. It is possible that the large size of Ad and LV particles (60-120 nm) prevents their efficient diffusion through the dense adult interphotoreceptor matrix (IPM) (Mieziewska, 1996). It is interesting that PR transduction by LVs has been reported to either positively Pang et al, 2006) or negatively (Calame et al, 2011) correlate with disease-associated or induced PR damage and to be improved by loosening the IPM (Gruter et al, 2005).…”