En Face Optical Coherence Tomography of Foveal Microstructure in Full-Thickness Macular Hole: A Model to Study Perifoveal Müller Cells

Abstract

INTRODUCTIONEn-face optical coherence tomography (OCT) is an emerging imaging modality that facilitates the assessment of retinal structures transversely.1,2 Available since 2006 on certain OCT devices, the first retinal transverse scans were difficult to analyze interpret as only plane sections of the concave retina were available. 3 More recently, Spectral-Domain OCT technology with advanced alignment algorithm have adjusted sections to a reference curve, which has allowed layer-by-layer retinal imaging and provided a new investigation tool for a range of retinal disorders. 4-9The foveal microstructure is formed by a dense compaction of cone photoreceptors and their projected axons, which are intertwined with retinal glial Müller cells and follow a centrifugal course towards the inner layers at the edges of the fovea. Retinal glial Müller cells are critical for retinal homeostasis, providing metabolic support to neighboring neural cells, delivering neuroactive substances and retinoids to cones, and recycling waste compounds. 10,11 Müller cells are 5 times more abundant in the macula than in the peripheral retina.12 The "Z-shape" morphology of perifoveal Müller cells has been observed on histological sections in both animal and human models, where the cells adopt three consecutive orientations (Figure 1). 13,14 From the internal limiting membrane, perifoveal Müller cells run vertically to the inner nuclear layer, then turn inwards towards the foveal center across the outer plexiform layer and the Henle's fiber layer where their course is oblique and almost horizontal in the internal portion of the foveal pit. Then, at the junction with the outer nuclear layer, they take a vertical orientation again to reach the external limiting membrane (Figure 1). At the external limiting membrane of the primate retina, Omri et al. have previously shown that Müller cells and photoreceptors are bound by tight-like junctions, where the proteins occludin and zonula occludens-1 are expressed. 15Intraretinal fluid accumulation disrupts the foveal architecture, presenting an opportunity to examine its components in better detail. In full-thickness macular hole (MH), intraretinal cysts are frequently observed on OCT around the edges of the hole. On fluorescein angiography, no vascular leakage or filling of the cysts is usually observed. 16 This suggests that they originate from a metabolic dysfunction and supports the hypothesis of Müller cells implication in the pathogenesis of fullthickness MH. [17][18][19] In this study, we use en face OCT to characterize and quantify layer by layer, the perifoveal cystic cavities occurring around full-thickness MHs. To support the OCT findings, we used human and non-human primate macular flat-mounts and sections to visualize Müller cells stained with a glial marker. METHODS SubjectsThis observational case series adhered to the tenets of the Declaration of Helsinki, and the need of approval was waived by the Institutional Review Board of the Nuovo Regina Margherita Hospital, due to its retrospect...

Correlations between intraretinal cystoid cavities and pre- and postoperative characteristics of eyes after closure of idiopathic macular hole

“…We measured the mean values of the area on the perpendicular images with OCT radial scans and confirmed that the horizontal and vertical images had the same cystoid cavities. However, some studies have evaluated the cystic areas in the en face OCT images, and similar measurements in our patients would probably lead to a more precise assessment of the cystic areas 29,31 . Third, the follow-up period was relatively short.…”

“…Previous study combining the immunohistochemistry with en face OCT images demonstrated the features of the cystoid cavities 29 www.nature.com/scientificreports www.nature.com/scientificreports/ Gass classified MHs by the extent of the vitreomacular adhesion: Stage 2, partial detachment of the posterior hyaloid; Stage 3, total detachment of the posterior hyaloid but still attached to the optic disc; and Stage 4, complete detachment of the posterior vitreous 1 . In our results, the Stage 3 eyes had significantly larger cystoid areas and higher ELM height than Stage 2 or Stage 4 MH eyes.…”

Spontaneous closure of small full‐thickness macular holes: Presumed role of Müller cells

“…; Matet et al. ). At the ELM, Müller cells contain contractile rings of filamentous actin which enclose the photoreceptors; these rings are associated with the junctions between Müller and photoreceptor cells and form a structural meshwork in which photoreceptors are embedded (Del et al.…”

Glia of the human retina

“…A steeper slope of the OLM can be also produced by a vertical contraction of the stalk of the Müller cell cone in the center of the foveola (Figure c) (Bringmann et al, ). The Müller cell‐mediated displacement of foveal photoreceptors is supported by tight‐like junctions between Müller and photoreceptor cells in the outer retina and at the OLM (Matet et al, ; Omri et al, ). This mechanism may be one basis of the remarkable capacity of photoreceptors to realign themselves towards the pupil after retinal detachment or pupil displacement (Enoch, van Loo Jr., & Okun, ).…”

“…The latter was suggested to be mediated by a radial contraction of the receptor segments and a horizontal contraction of Müller cell structures which surround the photoreceptor cells at the OLM (Bringmann et al, ; Provis, Dubis, Maddess, & Carroll, ). Photoreceptor and Müller cells are tightly glued together in the HFL and ONL, and at the OLM (Matet et al, ; Omri et al, ). At the OLM, Müller cells contain contractile rings of filamentous actin which enclose the photoreceptors; the rings are connected with the junctions between Müller and photoreceptor cells and form a structural meshwork in which photoreceptors are embedded (Del Priore, Lewis, Tan, Carley, & Webb, ).…”