scholarly journals Ultrathin micromolded 3D scaffolds for high-density photoreceptor layer reconstruction

2021 ◽  
Vol 7 (17) ◽  
pp. eabf0344
Author(s):  
In-Kyu Lee ◽  
Allison L. Ludwig ◽  
M. Joseph Phillips ◽  
Juhwan Lee ◽  
Ruosen Xie ◽  
...  
Keyword(s):  
Early Stage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Three Dimensional ◽  
High Density ◽  
Cell Delivery ◽  
Photoreceptor Layer ◽  
Nanoscale Structures ◽  
Polymeric Scaffolds ◽  
Ice Cube

Polymeric scaffolds are revolutionizing therapeutics for blinding disorders affecting the outer retina, a region anatomically and functionally defined by light-sensitive photoreceptors. Recent engineering advances have produced planar scaffolds optimized for retinal pigment epithelium monolayer delivery, which are being tested in early-stage clinical trials. We previously described a three-dimensional scaffold supporting a polarized photoreceptor monolayer, but photoreceptor somata typically occupy multiple densely packed strata to maximize light detection. Thus, patients with severe photoreceptor degeneration are expected to extract greater benefits from higher-density photoreceptor delivery. Here, we describe the microfabrication of a biodegradable scaffold patterned for high-density photoreceptor replacement. The “ice cube tray” structure optimizes mechanical properties and cell-to-biomaterial load, enabling production of a multicellular photoreceptor layer designed for outer retinal reconstruction. Our approach may also be useful in the production of a multitude of micro- and nanoscale structures for multilayered cell delivery in other tissues.

scholarly journals Restoration of visual function by transplantation of optogenetically engineered photoreceptors

2018 ◽  
Author(s):  
Marcela Garita-Hernandez ◽  
Maruša Lampič ◽  
Antoine Chaffiol ◽  
Laure Guibbal ◽  
Fiona Routet ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Pluripotent Stem Cells ◽  
Visual Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Level ◽  
Photoreceptor Layer ◽  
Chloride Pump ◽  
Retinal Degenerative Diseases ◽  
Induced Pluripotent

A major challenge in the treatment of retinal degenerative diseases, with the transplantation of replacement photoreceptors, is the difficulty in inducing the grafted cells to grow and maintain light sensitive outer segments (OS) in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). For a RPE-independent treatment approach, we introduced a hyperpolarizing microbial opsin into photoreceptor precursors from new-born mice, and transplanted them into blind mice lacking the photoreceptor layer. These optogenetically transformed photoreceptors were light responsive and their transplantation lead to the recovery of visual function, as shown by ganglion cell recordings and behavioral tests. Subsequently, we generated cone photoreceptors from human induced pluripotent stem cells (hiPSCs), expressing the chloride pump Jaws. After transplantation into blind mice, we observed light-driven responses at the photoreceptor and ganglion cell level. These results demonstrate that structural and functional retinal repair is possible by combining stem cell therapy and optogenetics.

scholarly journals Associations with photoreceptor thickness measures in the UK Biobank

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sharon Y. L. Chua ◽  
◽  
Baljean Dhillon ◽  
Tariq Aslam ◽  
Konstantinos Balaskas ◽  
...  
Keyword(s):  
Refractive Error ◽  
Smoking Status ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Corneal Hysteresis ◽  
Uk Biobank ◽  
External Limiting Membrane ◽  
Photoreceptor Layer ◽  
Sd Oct ◽  
Total Average

AbstractSpectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40–69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness.

scholarly journals Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Giovanna Carnovale Scalzo ◽  
Adriano Carnevali ◽  
Gabriele Piccoli ◽  
Domenico Ceravolo ◽  
Donatella Bruzzichessi ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Multimodal Imaging ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Unknown Origin ◽  
Clinical Findings ◽  
Macular Dystrophy ◽  
Photoreceptor Layer ◽  
Inherited Retinal Dystrophies ◽  
Italian Case

Abstract Background To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. Case presentation An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation. Conclusion Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.

scholarly journals Selective Ablation of Dehydrodolichyl Diphosphate Synthase in Murine Retinal Pigment Epithelium (RPE) Causes RPE Atrophy and Retinal Degeneration

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 771 ◽  
Author(s):  
Marci L. DeRamus ◽  
Stephanie J. Davis ◽  
Sriganesh Ramachandra Rao ◽  
Cyril Nyankerh ◽  
Delores Stacks ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Types ◽  
Protein Glycosylation ◽  
Photoreceptor Layer ◽  
Selective Ablation ◽  
Rpe Atrophy ◽  
Structural Loss

Patients with certain defects in the dehydrodolichyl diphosphate synthase (DHDDS) gene (RP59; OMIM #613861) exhibit classic symptoms of retinitis pigmentosa, as well as macular changes, suggestive of retinal pigment epithelium (RPE) involvement. The DHDDS enzyme is ubiquitously required for several pathways of protein glycosylation. We wish to understand the basis for selective ocular pathology associated with certain DHDDS mutations and the contribution of specific ocular cell types to the pathology of mutant Dhdds-mediated retinal degeneration. To circumvent embryonic lethality associated with Dhdds knockout, we generated a Cre-dependent knockout allele of murine Dhdds (Dhddsflx/flx). We used targeted Cre expression to study the importance of the enzyme in the RPE. Structural alterations of the RPE and retina including reduction in outer retinal thickness, cell layer disruption, and increased RPE hyper-reflectivity were apparent at one postnatal month. At three months, RPE and photoreceptor disruption was observed non-uniformly across the retina as well as RPE transmigration into the photoreceptor layer, external limiting membrane descent towards the RPE, and patchy loss of photoreceptors. Functional loss measured by electroretinography was consistent with structural loss showing scotopic a- and b-wave reductions of 83% and 77%, respectively, at three months. These results indicate that RPE dysfunction contributes to DHDDS mutation-mediated pathology and suggests a more complicated disease mechanism than simply disruption of glycosylation.

Semiquantitative Methods for GFP Immunohistochemistry and In Situ Hybridization to Evaluate AAV Transduction of Mouse Retinal Cells Following Subretinal Injection

2020 ◽  
pp. 019262332096480
Author(s):  
Gennadiy Bondarenko ◽  
Steven D. Sorden ◽  
Brian J. Christian ◽  
Sharron Webster ◽  
Alok K. Sharma
Keyword(s):  
In Situ Hybridization ◽  
Fluorescent Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Layer ◽  
Rna In Situ Hybridization ◽  
Semiquantitative Evaluation ◽  
Green Fluorescent ◽  
Subretinal Injection

The goal of this study was to develop methods for the evaluation of green fluorescent protein (GFP) and GFP transcript biodistribution in paraformaldehyde-fixed paraffin-embedded (PFPE) eye sections to assess the effectiveness of Adeno-associated virus (AAV) gene delivery in an experimental ocular toxicity study. Female C57BL/6NTac mice were administered AAV2-enhancedGFP vector once via subretinal injection. One group also received anti-inflammatory therapy (meloxicam). Immunohistochemistry (IHC) and RNA in situ hybridization (ISH) for GFP were performed on PFPE serial eye sections and evaluated using semiquantitative methods. On day 43, GFP labeling in both IHC and ISH sections was greatest in the retinal pigment epithelium, compared with other retinal layers in which expression was negative to moderate. Despite the presence of IHC GFP labeling in the photoreceptor layer (PRL) in some animals, only low numbers of transduced cells were detected by ISH in the PRL. Simultaneous analysis of IHC and ISH may be needed for comprehensive assessment of gene transduction and protein biodistribution. This study demonstrates approaches for semiquantitative evaluation of IHC and ISH that allow interpretation and reporting of GFP expression in toxicity studies.

scholarly journals Optical Coherence Tomography Findings (SD-OCT and OCTA) in Early-Stage Type 3 Neovascularization

2020 ◽  
Vol 11 (2) ◽  
pp. 493-499
Author(s):  
Nisa Silva ◽  
Ana Marta ◽  
Pedro Baptista ◽  
Maria João Furtado ◽  
Miguel Lume
Keyword(s):  
Optical Coherence Tomography ◽  
Early Stage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Optical Coherence ◽  
Outer Retina ◽  
Type 3 Neovascularization ◽  
Intraretinal Fluid ◽  
Type 3 ◽  
Sd Oct

A 76-year-old male presented with a small hyperreflective density in the outer nuclear layer with subtle retinal pigment epithelium (RPE) elevation and few intraretinal cysts on spectral-domain optical coherence tomography (SD-OCT). Optical coherence tomography angiography (OCTA) confirmed the presence of a tuft-shaped intraretinal neovascular lesion. SD-OCT performed 2 months before showed a smaller RPE elevation at the same location without intraretinal fluid. A 79-year-old male presented with a small hyperreflective density in the outer retina surrounded by scant intraretinal fluid on SD-OCT and a bright vessel on OCTA, suggesting early-stage type 3 neovascularization. SD-OCT performed 2 months before showed a smaller hyperreflectivity at the same location, without intraretinal fluid. An 84-year-old female presented with hyperreflective foci in the outer retina overlying a serous pigment epithelium detachment (PED) with focal RPE disruption on SD-OCT. SD-OCT performed 2 months before showed the same hyperreflective lesion associated with a shallower PED. No neovascular lesions were found on OCTA after six injections of bevacizumab. To conclude, careful evaluation of SD-OCT allows for early detection of type 3 neovascularization at a pre-exudative stage. OCTA may be useful in confirming the presence of intraretinal neovascular lesion and monitoring response to anti-vascular endothelial growth factor agents.

EVALUATION OF MODERN PROPHYLACTIC FEATURES IN RETINAL DEGENERATIVE PATHOLOGIES OF THE EYE

2021 ◽  
Vol 2 (3) ◽  
pp. 5-10
Author(s):  
Saida Egamberdiyeva ◽  
◽  
Sarvarkhon Yuldashov ◽  
Azamjon Korabaev ◽  
Namunahon Askarova
Keyword(s):  
Macular Degeneration ◽  
Primary Open Angle Glaucoma ◽  
Peripheral Vision ◽  
Open Angle Glaucoma ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Open Angle ◽  
Photoreceptor Layer ◽  
Age Related

Age-related macular degeneration (AMD) is a progressive eye disease in which the physiological function of the choriocapillaries, Bruch’s membrane, and retinal pigment epithelium (RPE) areimpaired, a defect in the photoreceptor layer occurs, and central vision is irreversible. Primary open-angle glaucoma (POAG)is a pathological process characterized by impaired hydrodynamicsof intraocular fluid and damage to the optic nerve, althoughthe anterior chamber angle is open. In this disease, intraocular pressure (IOP) often increases and peripheral vision decreases depending on the retinallayer's level of compression. According to WHO statistics, POAG is then complicated by the “dry” form of AMD in 41% of cases, i.e. an effectivecombination of the above two pathologies can be observed in clinical practice. Consumption of foods rich in antioxidant micronutrients and drugslikes“Ophthalmocomplex” in the prevention and treatment of chronic degenerative eye diseases such as primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) can shorten the rehabilitation period. Themechanisms of development of pathologicalprocesses (especially inflammation, degeneration) are different. Still,the main pathogenetic point is the disruption of the antioxidant defense system as a result of detoxification.Keywords: age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), vitamins, antioxidants, partially oxidized free radicals, Ophthalmocomplex drug, healthy eating

Sign in / Sign up

Export Citation Format

Share Document