Tissue Translocation Device for Surgical Correction of Age-Related Macular Degeneration

2013 ◽  
Vol 7 (4) ◽  
Author(s):  
George Mathai ◽  
David Rosen ◽  
Shreyes Melkote ◽  
Timothy Olsen
Keyword(s):  
Shape Memory ◽  
Macular Degeneration ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Potential Method ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world in those over age 60. While this disorder is complex, the origin of injury appears to be at the level of the retinal pigment epithelium (RPE), Bruchs membrane, and inner choroid. A potential method to replace damaged tissue in AMD is to harvest healthy donor tissue (RPE-Bruchs-Choroid) from an eye and translocate it to the injured subretinal region. Such an autograft avoids immune mediated rejection and can theoretically restore function to the neurosensory retina (light sensitive part of the retina) by restoring the damaged tissue. Such a procedure requires the design of a device that mechanically supports the integrity of the graft while inside the eye, without injuring or disrupting the tissue. This paper presents the systematic design and manufacture of a thin shape memory foil-based tissue translocation device. The selected embodiment of the design uses thermal adhesion of the tissue to the foil surfaces for tissue support. The shape memory effect enables insertion of the device into the eye via a small incision. The device is manufactured using micromachining techniques and has been tested both ex vivo and in vivo with acceptable anatomic results.

scholarly journals Choriocapillaris Loss in Advanced Age-Related Macular Degeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Carlos A. Moreira-Neto ◽  
Eric M. Moult ◽  
James G. Fujimoto ◽  
Nadia K. Waheed ◽  
Daniela Ferrara
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Tissue Loss ◽  
Age Related

The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy. Others have hypothesized that deposition of complement complexes on and around the choriocapillaris could be related to the tissue loss observed in early AMD. The development of imaging modalities, such as optical coherence tomography angiography (OCTA), have led to a better understanding of underlying physiopathological mechanisms in AMD. OCTA showed atrophy of choriocapillaris underneath and beyond the region of photoreceptors and RPE loss, in agreement with previous histopathologic studies. The evolution of OCTA technology suggests that CNV seems to originate from regions of severe choriocapillaris alteration. Significant progress has been made in the understanding of development and progression of GA and CNV. In vivo investigation of the choriocapillaris using OCTA may lead to new insights related to underlying disease mechanisms in AMD.

scholarly journals A Potential New Role for Zinc in Age-Related Macular Degeneration through Regulation of Endothelial Fenestration

2021 ◽  
Vol 22 (21) ◽  
pp. 11974
Author(s):  
Fiona Cunningham ◽  
Sabrina Cahyadi ◽  
Imre Lengyel
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Uniform Size ◽  
Age Related ◽  
Typical Morphology ◽  
Fenestrated Endothelium ◽  
Zinc Concentrations

Age-related macular degeneration (AMD) is a common blinding disease in the western world that is linked to the loss of fenestration in the choriocapillaris that sustains the retinal pigment epithelium and photoreceptors in the back of the eye. Changes in ocular and systemic zinc concentrations have been associated with AMD; therefore, we hypothesized that these changes might be directly involved in fenestrae formation. To test this hypothesis, an endothelial cell (bEND.5) model for fenestrae formation was treated with different concentrations of zinc sulfate (ZnSO4) solution for up to 20 h. Fenestrae were visualized by staining for Plasmalemmal Vesicle Associated Protein-1 (PV-1), the protein that forms the diaphragms of the fenestrated endothelium. Size and distribution were monitored by transmission electron microscopy (TEM). We found that zinc induced the redistribution of PV-1 into areas called sieve plates containing ~70-nm uniform size and typical morphology fenestrae. As AMD is associated with reduced zinc concentrations in the serum and in ocular tissues, and dietary zinc supplementation is recommended to slow disease progression, we propose here that the elevation of zinc concentration may restore choriocapillaris fenestration resulting in improved nutrient flow and clearance of waste material in the retina.

scholarly journals Ex Vivo Hyperspectral Autofluorescence Imaging and Localization of Fluorophores in Human Eyes with Age-Related Macular Degeneration

Vision ◽  
2018 ◽  
Vol 2 (4) ◽  
pp. 38
Author(s):  
Taariq Mohammed ◽  
Yuehong Tong ◽  
Julia Agee ◽  
Nayanika Challa ◽  
Rainer Heintzmann ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Emission Spectra ◽  
Age Related Macular Degeneration ◽  
Autofluorescence Imaging ◽  
Age Related ◽  
Human Eyes ◽  
Similar Peak

To characterize fluorophore signals from drusen and retinal pigment epithelium (RPE) and their changes in age related macular degeneration (AMD), the authors describe advances in ex vivo hyperspectral autofluorescence (AF) imaging of human eye tissue. Ten RPE flatmounts from eyes with AMD and 10 from eyes without AMD underwent 40× hyperspectral AF microscopic imaging. The number of excitation wavelengths tested was initially two (436 nm and 480 nm), then increased to three (436 nm, 480 nm, and 505 nm). Emission spectra were collected at 10 nm intervals from 420 nm to 720 nm. Non-negative matrix factorization (NMF) algorithms decomposed the hyperspectral images into individual emission spectra and their spatial abundances. These include three distinguishable spectra for RPE fluorophores (S1, S2, and S3) in both AMD and non-AMD eyes, a spectrum for drusen (SDr) only in AMD eyes, and a Bruch’s membrane spectrum that was detectable in normal eyes. Simultaneous analysis of datacubes excited atthree excitation wavelengths revealed more detailed spatial localization of the RPE spectra and SDr within drusen than exciting only at two wavelengths. Within AMD and non-AMD groups, two different NMF initialization methods were tested on each group and converged to qualitatively similar spectra. In AMD, the peaks of the SDr at ~510 nm (436 nm excitation) were particularly consistent. Between AMD and non-AMD groups, corresponding spectra in common, S1, S2, and S3, also had similar peak locations and shapes, but with some differences and further characterization warranted.

scholarly journals Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9356
Author(s):  
Yara A. Samra ◽  
Dina Kira ◽  
Pragya Rajpurohit ◽  
Riyaz Mohamed ◽  
Leah A. Owen ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Aspartate Receptor ◽  
Age Related ◽  
Retinal Structure

Age-related macular degeneration (AMD) is a leading cause of vision loss. Elevated homocysteine (Hcy) (Hyperhomocysteinemia) (HHcy) has been reported in AMD. We previously reported that HHcy induces AMD-like features. This study suggests that N-Methyl-d-aspartate receptor (NMDAR) activation in the retinal pigment epithelium (RPE) is a mechanism for HHcy-induced AMD. Serum Hcy and cystathionine-β-synthase (CBS) were assessed by ELISA. The involvement of NMDAR in Hcy-induced AMD features was evaluated (1) in vitro using ARPE-19 cells, primary RPE isolated from HHcy mice (CBS), and mouse choroidal endothelial cells (MCEC); (2) in vivo using wild-type mice and mice deficient in RPE NMDAR (NMDARR-/-) with/without Hcy injection. Isolectin-B4, Ki67, HIF-1α, VEGF, NMDAR1, and albumin were assessed by immunofluorescence (IF), Western blot (WB), Optical coherence tomography (OCT), and fluorescein angiography (FA) to evaluate retinal structure, fluorescein leakage, and choroidal neovascularization (CNV). A neovascular AMD patient’s serum showed a significant increase in Hcy and a decrease in CBS. Hcy significantly increased HIF-1α, VEGF, and NMDAR in RPE cells, and Ki67 in MCEC. Hcy-injected WT mice showed disrupted retina and CNV. Knocking down RPE NMDAR improved retinal structure and CNV. Our findings underscore the role of RPE NMDAR in Hcy-induced AMD features; thus, NMDAR inhibition could serve as a promising therapeutic target for AMD.

In Vivo Multimodal Retinal Imaging Correlates With Granular-specific Changes in the Organelles of Retinal Pigment Epithelium of a Murine Model of Stargardt Disease

2021 ◽  
Author(s):  
Ratheesh K. Meleppat ◽  
Kaitryn E. Ronning ◽  
Sarah J. Karlen ◽  
Marie E. Burns ◽  
Edward N. Pugh ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Stargardt Disease ◽  
Rpe Cells ◽  
Age Related ◽  
Lipofuscin Granules

Abstract Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of granular pigmented organelles found in the retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin granules in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study the disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4-/- mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess the melanosome density in vivo, whereas the AF images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize the lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased number of melanosomes in the RPE of Abca4-/- mice and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo in the two mouse strains.

scholarly journals In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

2013 ◽  
Vol 4 (11) ◽  
pp. 2527 ◽  
Author(s):  
Ethan A. Rossi ◽  
Piero Rangel-Fonseca ◽  
Keith Parkins ◽  
William Fischer ◽  
Lisa R. Latchney ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
In Vivo Imaging ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

scholarly journals Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Alexandra A. Herzlich ◽  
Jingsheng Tuo ◽  
Chi-Chao Chan
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Disease Process ◽  
Ppar Gamma ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of new blindness in the western world and is becoming more of a socio-medical problem as the proportion of the aged population increases. There are multiple efforts underway to better understand this disease process. AMD involves the abnormal retinal pigment epithelium (RPE), drusen formation, photoreceptor atrophy, and choroidal neovascularization. Peroxisome proliferator-activated receptors (PPARs) play an important role in lipid degeneration, immune regulation, regulation of reactive oxygen species (ROSs), as well as regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and docosahexaenoic acid (DHA). These molecules have all been implicated in the pathogenesis of AMD. In addition, PPAR gamma is expressed in RPE, an essential cell in photoreceptor regeneration and vision maintenance. This review summarizes the interactions between PPAR, AMD-related molecules, and AMD-related disease processes.

scholarly journals In vivo multimodal retinal imaging of disease-related pigmentary changes in retinal pigment epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ratheesh K. Meleppat ◽  
Kaitryn E. Ronning ◽  
Sarah J. Karlen ◽  
Marie E. Burns ◽  
Edward N. Pugh ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Stargardt Disease ◽  
Rpe Cells ◽  
Age Related ◽  
Lipofuscin Granules

AbstractMelanosomes, lipofuscin, and melanolipofuscin are the three principal types of pigmented granules found in retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4−/− mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess melanosome density in vivo, whereas the autofluorescence (AF) images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased concentration of melanosomes in the RPE of Abca4−/− mice, and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo between the two mouse strains.

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