Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease

Abstract

Interphotoreceptor retinoid-binding protein (IRBP), also known as retinol binding protein 3 (RBP3), is a lipophilic glycoprotein specifically secreted by photoreceptors. Enriched in the interphotoreceptor matrix (IPM) and recycled by the retinal pigment epithelium (RPE), IRBP is essential for the vision of all vertebrates as it facilitates the transfer of retinoids in the visual cycle. It also helps to transport lipids between the RPE and photoreceptors. The thiol-dependent antioxidant activity of IRBP maintains the delicate redox balance in the normal retina. Thus, its dysfunction is suspected to play a role in many retinal diseases. We have reviewed here the latest research on IRBP in both retinal health and disease, including the function and regulation of IRBP under retinal stress in both animal models and the human retina. We have also explored the therapeutic potential of targeting IRBP in retinal diseases. Although some technical barriers remain, it is possible that manipulating the expression of IRBP in the retina will rescue or prevent photoreceptor degeneration in many retinal diseases.

Depletion of Retinal Dopaminergic Activity in a Mouse Model of Rod Dysfunction Exacerbates Experimental Autoimmune Uveoretinitis: A Role for the Gateway Reflex

“…The other issue to consider in the reduction of retinal DA levels is rod photoreceptor degeneration in the EAU model induced by active immunization with IRBP. The IRBP constitutes most of the extracellular matrix present between the photoreceptors and the retinal pigment epithelium [ 77 ]. Thus, in this EAU model, the infiltration of pathogenic CD4+ T cells that mediate an autoimmune response against IRBP, combined with the accumulation of subretinal fluid caused by BRB breakdown, results in the destruction of photoreceptors [ 28 , 29 , 77 , 78 , 79 ].…”

“…The IRBP constitutes most of the extracellular matrix present between the photoreceptors and the retinal pigment epithelium [ 77 ]. Thus, in this EAU model, the infiltration of pathogenic CD4+ T cells that mediate an autoimmune response against IRBP, combined with the accumulation of subretinal fluid caused by BRB breakdown, results in the destruction of photoreceptors [ 28 , 29 , 77 , 78 , 79 ]. However, although the EAU-induced disruption of the retinal ONL structure, reflecting photoreceptor loss, was extensive in Gnat1 rd17 mice, the retinal DA levels were higher in EAU Gnat1 rd17 mice compared to age-matched Gnat1 rd17 mice without EAU and signs of photoreceptor degeneration.…”

Acute and chronic blood serum proteome changes in patients with methanol poisoning

“…The increased concentrations of RBP in our study are in contrast to previous ethanol-consumption based studies. It is not known whether these higher levels of retinol-binding protein concentrations during methanol intoxication are only a side-effect of broken retinol transport and metabolism in retinal epithelium cells, other retina damage, or some kind of protective effect (see 86 – 90 ).…”

The Role of Vitamin A in Retinal Diseases

“…11-cis-retinal is then released into the interphotoreceptor matrix, where it binds interphotoreceptor retinoid-binding protein (IRBP), which delivers it to the outer segments of photoreceptors. There 11-cis-retinal combines with opsin to form visual pigment [47,50,51] (Figure 1). The visual pigments in rods and cones are rhodopsin (RHO) and iodopsin, respectively.…”

“…It is secreted by photoreceptors and accumulates in the interphotoreceptor matrix. It functions as the transporter of retinoids between the photoreceptors and RPE and also between photoreceptors and Müller cells [29,50,66,166]. Pathogenic variants in RBP3 gene are described as an infrequent cause of autosomal recessive RP [167].…”