Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells

Abstract

The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions.

Bestrophinopathy: An RPE-photoreceptor interface disease

“…Despite the fact that IPM occupies a strategic location in the retina, for many years it was considered as an amorphous substance of unknown function and significance. We now know that this intricate yet highly organized structure with interconnected domains designed to meet the specific needs of both rods and cones, is critical for maintaining the homeostatic milieu of subretinal space and formation of an adhesive bond between RPE and photoreceptors (Johnson and Hageman, 1991; Mieziewska et al, 1993; Ishikawa et al 2015). The key location between RPE apical surface and photoreceptors allows IPM to fulfill a range of biochemical and physical tasks fundamental for normal retinal function, among which the most critical ones like regulation of oxygen, nutrients and retinoid transport or preservation of cytoskeleton and retinal adhesion by providing electrostatic support for photoreceptors (Johnson and Hageman, 1991; Mieziewska et al, 1993; Hauck et al, 2005; Ishikawa et al 2015).…”

“…We now know that this intricate yet highly organized structure with interconnected domains designed to meet the specific needs of both rods and cones, is critical for maintaining the homeostatic milieu of subretinal space and formation of an adhesive bond between RPE and photoreceptors (Johnson and Hageman, 1991; Mieziewska et al, 1993; Ishikawa et al 2015). The key location between RPE apical surface and photoreceptors allows IPM to fulfill a range of biochemical and physical tasks fundamental for normal retinal function, among which the most critical ones like regulation of oxygen, nutrients and retinoid transport or preservation of cytoskeleton and retinal adhesion by providing electrostatic support for photoreceptors (Johnson and Hageman, 1991; Mieziewska et al, 1993; Hauck et al, 2005; Ishikawa et al 2015). It is therefore not unexpected that any genetic or metabolic defect found in the soluble and insoluble components of IPM play a role in the etiology of retinal degenerative disorders, such as IMPG1-and IMPG2-associated vitelliform macular dystrophy (Manes et al, 2013; Meunier et al, 2014; Ishikawa et al 2015).…”

Underdeveloped RPE Apical Domain Underlies Lesion Formation in Canine Bestrophinopathies

“…As evinced by numerous studies, IPM is critical for maintaining the homeostatic milieu of the subretinal space, serving a range of biochemical and physical functions; these include the regulation of oxygen, nutrients, and retinoid transport, preservation of retinal adhesion by providing electrostatic support for photoreceptors, and participating in cytoskeletal organization in the surrounding cells (Ishikawa et al 2015). Thus, together with the impaired microvillar ensheathment, the compromised IPM accounts for the two major pathological culprits responsible for weakening of the RPE-neuroretina interactions in bestrophinopathies.…”

Effects of Ranibizumab and Aflibercept on Human Müller Cells and Photoreceptors under Stress Conditions

“…IRBP is a major soluble glycoprotein secreted by photoreceptors [51]. It is distributed within the interphotoreceptor matrix (IPM) in a light-dependent manner and participates in the intimate interactions between the IPM and photoreceptors [52]. IRBP is important for the maintenance of the function of photoreceptors through transport of 11- cis retinal and all- trans retinol between the photoreceptors and RPE cells in the visual cycle, buffering excess vitamin A in the IPM and protecting retinoids from degradation [52].…”

“…It is distributed within the interphotoreceptor matrix (IPM) in a light-dependent manner and participates in the intimate interactions between the IPM and photoreceptors [52]. IRBP is important for the maintenance of the function of photoreceptors through transport of 11- cis retinal and all- trans retinol between the photoreceptors and RPE cells in the visual cycle, buffering excess vitamin A in the IPM and protecting retinoids from degradation [52]. IRBP deficiency has been linked to photoreceptor damage in a number of retinal diseases including inherited retinal diseases [53] and diabetic retinopathy [31].…”