The Retinal Pigment Epithelium Apical Microvilli and Retinal Function

Bonilha, Vera L.; Rayborn, Mary E.; Bhattacharya, Sanjoy K.; Gu, X.; Crabb, John S.; Crabb, John W.; Hollyfield, Joe G.

doi:10.1007/0-387-32442-9_72

Cited by 49 publications

(41 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the outer segment, the presence of two bands can be explained by the microvilli of the RPE ensheathing only the most peripheral part of the outer segment of the PR. In humans, these microvilli can indeed extend for as long as half of the outer segment [27]. The RPE and the PR layers are thus entangled into one another, which may explain at least partly the poor contrast observed by SD-OCT between these two layers.…”

Section: Discussionmentioning

confidence: 99%

Spectral-Domain Optical Coherence Tomography of the Rodent Eye: Highlighting Layers of the Outer Retina Using Signal Averaging and Comparison with Histology

Berger

Cavallero²,

Domı́nguez³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Spectral-Domain Optical Coherence Tomography (SD-OCT) is a widely used method to observe retinal layers and follow pathological events in human. Recently, this technique has been adapted for animal imaging. This non-invasive technology brings a cross-sectional visualization of the retina, which permits to observe precisely each layer. There is a clear expansion of the use of this imaging modality in rodents, thus, a precise characterization of the different outer retinal layers observed by SD-OCT is now necessary to make the most of this technology. The identification of the inner strata until the outer nuclear layer has already been clearly established, while the attribution of the layers observed by SD-OCT to the structures corresponding to photoreceptors segments and retinal pigment epithelium is much more questionable. To progress in the understanding of experimental SD-OCT imaging, we developed a method for averaging SD-OCT data to generate a mean image allowing to better delineate layers in the retina of pigmented and albino strains of mice and rats. It allowed us to locate precisely the interface between photoreceptors and retinal pigment epithelium and to identify unambiguously four layers corresponding to the inner and outer parts of photoreceptors segments. We show that the thickness of the various layers can be measured as accurately in vivo on SD-OCT images, than post-mortem by a morphometric analysis of histological sections. We applied SD-OCT to different models and demonstrated that it allows analysis of focal or diffuse retinal pathological processes such as mutation-dependant damages or light-driven modification of photoreceptors. Moreover, we report a new method of combined use of SD-OCT and integration to quantify laser-induced choroidal neovascularization. In conclusion, we clearly demonstrated that SD-OCT represents a valuable tool for imaging the rodent retina that is at least as accurate as histology, non-invasive and allows longitudinal follow-up of the same animal.

show abstract

Section: Discussionmentioning

confidence: 99%

Spectral-Domain Optical Coherence Tomography of the Rodent Eye: Highlighting Layers of the Outer Retina Using Signal Averaging and Comparison with Histology

Berger

Cavallero²,

Domı́nguez³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The structural abnormalities related to the impaired microvillar ensheathment of photoreceptor outer segment tips and compromised insoluble IPM constitute two major pathological culprits responsible for weakening of the RPE-neuroretina physical and electrostatic interactions (Mieziewska, 1996; Bonilha et al, 2006). 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.…”

Section: Bestrophinopathy: An Rpe-photoreceptor Interface Diseasementioning

confidence: 99%

Bestrophinopathy: An RPE-photoreceptor interface disease

Guziewicz

Sinha

Gómez

et al. 2017

Progress in Retinal and Eye Research

View full text Add to dashboard Cite

Bestrophinopathies, one of the most common forms of inherited macular degenerations, are caused by mutations in the BEST1 gene expressed in the retinal pigment epithelium (RPE). Both human and canine BEST1-linked maculopathies are characterized by abnormal accumulation of autofluorescent material within RPE cells and bilateral macular or multifocal lesions; however, the specific mechanism leading to the formation of these lesions remains unclear. We now provide an overview of the current state of knowledge on the molecular pathology of bestrophinopathies, and explore factors promoting formation of RPE-neuroretinal separations, using the first spontaneous animal model of BEST1-associated retinopathies, canine Best (cBest). Here, we characterize the nature of the autofluorescent RPE cell inclusions and report matching spectral signatures of RPE-associated fluorophores between human and canine retinae, indicating an analogous composition of endogenous RPE deposits in Best Vitelliform Macular Dystrophy (BVMD) patients and its canine disease model. This study also exposes a range of biochemical and structural abnormalities at the RPE-photoreceptor interface related to the impaired cone-associated microvillar ensheathment and compromised insoluble interphotoreceptor matrix (IPM), the major pathological culprits responsible for weakening of the RPE-neuroretina interactions, and consequently, formation of vitelliform lesions. These salient alterations detected at the RPE apical domain in cBest as well as in BVMD- and ARB-hiPSC-RPE model systems provide novel insights into the pathological mechanism of BEST1-linked disorders that will allow for development of critical outcome measures guiding therapeutic strategies for bestrophinopathies.

show abstract

“…On its apical side, the RPE extends numerous microvilli around the light-sensitive photoreceptor outer segments and into the interphotoreceptor matrix. Microvilli considerably increase the surface area of the RPE apical membrane, and establish a critical interface for many RPE functions including phagocytosis of shed outer segments, visual chromophore transport and regeneration, production of trophic and antiangiogenic factors, directional transport of oxygen and nutrients from the choroid to sustain the high metabolic rate of photoreceptors, and removal of water and aqueous waste products from the subretinal space (Strauss, 2005;Bonilha et al, 2006). Mutations in genes expressed in RPE cells can result in retinal degeneration and loss of vision (Sparrow et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy for Retinitis Pigmentosa Caused by MFRP Mutations: Human Phenotype and Preliminary Proof of Concept

et al. 2012

View full text Add to dashboard Cite

Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy.

show abstract

The Retinal Pigment Epithelium Apical Microvilli and Retinal Function

Cited by 49 publications

References 32 publications

Spectral-Domain Optical Coherence Tomography of the Rodent Eye: Highlighting Layers of the Outer Retina Using Signal Averaging and Comparison with Histology

Spectral-Domain Optical Coherence Tomography of the Rodent Eye: Highlighting Layers of the Outer Retina Using Signal Averaging and Comparison with Histology

Bestrophinopathy: An RPE-photoreceptor interface disease

Gene Therapy for Retinitis Pigmentosa Caused by MFRP Mutations: Human Phenotype and Preliminary Proof of Concept

Contact Info

Product

Resources

About