scholarly journals Fission of megamitochondria into multiple smaller well-defined mitochondria in the ageing zebrafish retina

2021 ◽  
Author(s):  
Thomas Burgoyne ◽  
Maria Toms ◽  
Chris Way ◽  
Dhani Tracey-White ◽  
Clare Futter ◽  
...  
Keyword(s):  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Model Organism ◽  
Retinal Diseases ◽  
Future Studies ◽  
Temporal Gene Expression ◽  
Transmission Electron ◽  
Vertebrate Model ◽  
Cellular Organelles

Mitochondria are essential adenosine triphosphate (ATP)-generating cellular organelles. In the retina, they are highly numerous in the photoreceptors and retinal pigment epithelium (RPE) due to their high energetic requirements. Fission and fusion of the mitochondria within these cells allow them to adapt to changing demands over the lifespan of the organism. Using transmission electron microscopy, we examined the mitochondrial ultrastructure of zebrafish photoreceptors and RPE from 5 days post fertilisation (dpf) through to late adulthood (3 years). Notably, mitochondria in the youngest animals were large and irregular shaped with a loose cristae architecture, but by 8 dpf they had reduced in size and expanded in number with more defined cristae. When investigating temporal gene expression of several mitochondrial-related markers, they indicated fission as the dominant mechanism contributing to these changes observed over time. This is likely to be due to continued mitochondrial stress resulting from the oxidative environment of the retina and prolonged light exposure. We have characterised retinal mitochondrial ageing in a key vertebrate model organism, that provides a basis for future studies of retinal diseases that are linked to mitochondrial dysfunction.

scholarly journals Fine structure of the retinal pigment epithelium and cones of Antarctic fish Notohenia coriiceps Richardson in light and dark-conditions

2007 ◽  
Vol 24 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Lucélia Donatti ◽  
Edith Fanta
Keyword(s):  
Epithelial Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Antarctic Fish ◽  
Basal Region ◽  
Dense Cytoplasm ◽  
Transmission Electron ◽  
Notothenia Coriiceps ◽  
The Antarctic ◽  
Pigment Epithelial Cells

The Antarctic fish Notothenia coriiceps Richardson, 1844 lives in an environment of daily and annual photic variation and retina cells have to adjust morphologically to environmental luminosity. After seven day dark or seven day light acclimation of two groups of fish, retinas were extracted and processed for light and transmission electron microscopy. In seven day dark adapted, retina pigment epithelium melanin granules were aggregated at the basal region of cells, and macrophages were seen adjacent to the apical microvilli, between the photoreceptors. In seven day light adapted epithelium, melanin granules were inside the apical microvilli of epithelial cells and macrophages were absent. The supranuclear region of cones adapted to seven day light had less electron dense cytoplasm, and an endoplasmic reticulum with broad tubules. The mitochondria in the internal segment of cones adapted to seven day light were larger, and less electron dense. The differences in the morphology of cones and pigment epithelial cells indicate that N. coriiceps has retinal structural adjustments presumably optimizing vision in different light conditions.

scholarly journals Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

2021 ◽  
Vol 22 (17) ◽  
pp. 9618
Author(s):  
Jérémie Canonica ◽  
Min Zhao ◽  
Tatiana Favez ◽  
Emmanuelle Gelizé ◽  
Laurent Jonet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Pathway Activation ◽  
And Migration

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

scholarly journals Beyond AREDS Formulations, What Is Next for Intermediate Age-Related Macular Degeneration (iAMD) Treatment? Potential Benefits of Antioxidant and Anti-inflammatory Apocarotenoids as Neuroprotectors

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Serge Camelo ◽  
Mathilde Latil ◽  
Stanislas Veillet ◽  
Pierre J. Dilda ◽  
René Lafont
Keyword(s):  
Macular Degeneration ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Crocus Sativus ◽  
Subretinal Space ◽  
Major Health Problem ◽  
Age Related

Age-related macular degeneration (AMD) is the commonest cause of severe visual loss and blindness in developed countries among individuals aged 60 and older. AMD slowly progresses from early AMD to intermediate AMD (iAMD) and ultimately late-stage AMD. Late AMD encompasses either neovascular AMD (nAMD) or geographic atrophy (GA). nAMD is defined by choroidal neovascularization (CNV) and hemorrhage in the subretinal space at the level of the macula. This induces a rapid visual impairment caused by the death of photoreceptor cells. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibodies is the standard treatment of nAMD but adds to the burden of patient care. GA is characterized by slowly expanding photoreceptor, and retinal pigment epithelium (RPE) degeneration patches progressively leading to blindness. There is currently no therapy to cure GA. Late AMD continues to be an unmet medical need representing a major health problem with millions of patients worldwide. Oxidative stress and inflammation are recognized as some of the main risk factors to developing late AMD. The antioxidant formulation AREDS (Age-Related Eye Disease Studies), contains β-carotene, which has been replaced by lutein and zeaxanthin in AREDS2, are given to patients with iAMD but have a limited effect on the incidence of nAMD and GA. Thus, to avoid or slowdown the development of late stages of AMD (nAMD or GA), new therapies targeting iAMD are needed such as crocetin obtained through hydrolysis of crocin, an important component of saffron (Crocus sativus L.), and norbixin derived from bixin extracted from Bixa orellana seeds. We have shown that these apocarotenoids preserved more effectively RPE cells against apoptosis following blue light exposure in the presence of A2E than lutein and zeaxanthin. In this review, we will discuss the potential use of apocarotenoids to slowdown the progression of iAMD, to reduce the incidence of both forms of late AMD.

Normative pattern and determinants of outer retinal thickness in an Asian population: the Singapore Epidemiology of Eye Diseases Study

2019 ◽  
Vol 103 (10) ◽  
pp. 1406-1412 ◽  
Author(s):  
Wei Dai ◽  
Yih-Chung Tham ◽  
Miao-Li Chee ◽  
Shivani Majithia ◽  
Nicholas Y Q Tan ◽  
...  
Keyword(s):  
Retinal Thickness ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Plexiform Layer ◽  
Asian Population ◽  
Final Analysis ◽  
Population Based ◽  
Eye Diseases ◽  
Retinal Diseases ◽  
Sd Oct

Background/aimsTo evaluate the distribution and determinants of outer retinal thickness in eyes without retinal diseases, using spectral-domain optical coherence tomography (SD-OCT).MethodsParticipants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians in Singapore. A total of 5333 participants underwent SD-OCT imaging in which a 6×6 mm2 measurement area centred at the fovea. Outer retinal thickness was defined as the distance from the outer plexiform layer to the retinal pigment epithelium layer boundary.Results7444 eyes from 4454 participants were included in final analysis. Of them, mean age was 58.4 years (SD 8.3), and 2294 (51.5%) were women. Women (121.0±8.1 µm) had thinner average outer retinal thickness than men (125.6±8.2 µm) (p<0.001). Malays (121.4±8.7 µm) had thinner average outer retinal thickness than Indians (124.3±8.6 µm) and Chinese (123.7±7.9 µm) (both p<0.001). In multivariable models, thinner average outer retinal thickness was associated with older age (per decade, β=−1.02, p<0.001), hypertension (β=−0.59, p=0.029), diabetes (β=−0.73, p=0.013), chronic kidney disease (β=−1.25, p=0.017), longer axial length (per mm, β=−0.76, p<0.001), flatter corneal curvature (per mm, β=−2.00, p<0.001) and higher signal strength (β=−1.46, p<0.001).ConclusionIn this large sample of Asian population, we provided normative SD-OCT data on outer retinal thickness in eyes without retinal diseases. Women had thinner outer retina than men. For the first time, these findings provide fundamental knowledge on normative profile of outer retinal thickness in Asians.

Effect ofToxoplasma gondiiinfection on the junctional complex of retinal pigment epithelial cells

Parasitology ◽  
2016 ◽  
Vol 143 (5) ◽  
pp. 568-575 ◽  
Author(s):  
ALANDERSON R. NOGUEIRA ◽  
FERNANDA LEVE ◽  
JOSÉ MORGADO-DIAZ ◽  
ROBERTO CARLOS TEDESCO ◽  
MIRIAN CLAUDIA S. PEREIRA
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Ocular Toxoplasmosis ◽  
Junctional Complex ◽  
Cell Contact ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Retinal Injury ◽  
Transmission Electron

SUMMARYOcular toxoplasmosis is the most frequent cause of uveitis, leading to partial or total loss of vision, with the retina the main affected structure. The cells of the retinal pigment epithelium (RPE) play an important role in the physiology of the retina and formation of the blood–retinal barrier. Several pathogens induce barrier dysfunction by altering tight junction (TJ) integrity. Here, we analysed the effect of infection byToxoplasma gondiion TJ integrity in ARPE-19 cells. Loss of TJ integrity was demonstrated inT. gondii-infected ARPE-19 cells, causing increase in paracellular permeability and disturbance of the barrier function of the RPE. Confocal microscopy also revealed alteration in the TJ protein occludin induced byT. gondiiinfection. Disruption of junctional complex was also evidenced by scanning and transmission electron microscopy. Cell–cell contact loss was noticed in the early stages of infection byT. gondiiwith the visualization of small to moderate intercellular spaces. Large gaps were mostly observed with the progression of the infection. Thus, our data suggest that the alterations induced byT. gondiiin the structural organization of the RPE may contribute to retinal injury evidenced by ocular toxoplasmosis.

scholarly journals Degradation of Photoreceptor Outer Segments by the Retinal Pigment Epithelium Requires Pigment Epithelium-derived Factor Receptor (PEDF-R)

2021 ◽  
Author(s):  
Jeanee Bullock ◽  
Federica Polato ◽  
Mones Abu-Asab ◽  
Alexandra Bernardo-Colón ◽  
Elma Aflaki ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Phospholipase A2 ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Outer Segment ◽  
Western Blots ◽  
Rpe Cells ◽  
Photoreceptor Outer Segments ◽  
Transmission Electron ◽  
Bromoenol Lactone

AbstractPurposeTo examine the contribution of PEDF-R to the phagocytosis process. Previously, we identified PEDF-R, the protein encoded by the PNPLA2 gene, as a phospholipase A2 in the retinal pigment epithelium (RPE). During phagocytosis, RPE cells ingest abundant phospholipids and protein in the form of photoreceptor outer segment (POS) tips, which are then hydrolyzed. The role of PEDF-R in RPE phagocytosis is not known.MethodsMice in which PNPLA2 was conditionally knocked out in the RPE were generated (cKO). Mouse RPE/choroid explants were cultured. Human ARPE-19 cells were transfected with siPNPLA2 silencing duplexes. POS were isolated from bovine retinas. The phospholipase A2 inhibitor bromoenol lactone was used. Transmission electron microscopy, immunofluorescence, lipid labeling, pulse-chase experiments, western blots, and free fatty acid and β-hydroxybutyrate assays were performed.ResultsThe RPE of the cKO mice accumulated lipids as well as more abundant and larger rhodopsin particles compared to littermate controls. Upon POS exposure, RPE explants from cKO mice released less β-hydroxybutyrate compared to controls. After POS ingestion during phagocytosis, rhodopsin degradation was stalled both in cells treated with bromoenol lactone and in PNPLA2-knocked-down cells relative to their corresponding controls. Phospholipase A2 inhibition lowered β-hydroxybutyrate release from phagocytic RPE cells. PNPLA2 knock down also resulted in a decline in fatty acids and β-hydroxybutyrate release from phagocytic RPE cells.ConclusionsPEDF-R downregulation delayed POS digestion during phagocytosis. The findings imply that efficiency of RPE phagocytosis depends on PEDF-R, thus identifying a novel contribution of this protein to POS degradation in the RPE.

scholarly journals The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Complex Structure ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Strong Connection ◽  
Age Related

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

Noninvasive recording and response characteristics of the rat dc-electroretinogram

2002 ◽  
Vol 19 (6) ◽  
pp. 693-701 ◽  
Author(s):  
NEAL S. PEACHEY ◽  
J. BRETT STANTON ◽  
ALAN D. MARMORSTEIN
Keyword(s):  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Experimental Manipulation ◽  
Sprague Dawley ◽  
Active Electrode ◽  
Slow Potential ◽  
Full Field ◽  
Stimulus Response ◽  
Response Characteristics

In response to light, the retinal pigment epithelium (RPE) generates a series of potentials that can be recorded using the dc-electroretinogram (dc-ERG). As these potentials can be related to specific cellular events, they provide information about RPE function and how that may be altered by disease or experimental manipulation. The purposes of the present study were to define a noninvasive means for recording the rat dc-ERG, to use this to define the stimulus–response properties of the major components, and to relate these results to measures of the rat electrooculogram (EOG). Parallel studies were conducted in two strains of rats (Long-Evans, LE; Sprague-Dawley, SD) that are commonly used in vision research. Rats were sedated with ketamine/xylazine and placed on a heating pad. Ag/AgCl wire electrodes were bridged with capillary tubes filled with Hanks balanced salt solution. The active electrode was placed in contact with the corneal surface and referenced to a second electrode placed within the orbit. The dc-ERG signal was amplified (dc-100 Hz), digitized, and stored offline. The duration of full-field flash stimuli was controlled using a mechanical shutter and flash luminance was controlled with neutral density filters. EOGs were recorded using subdermal platinum needle electrodes placed near the eye. In response to a 5-min light exposure, the dc-ERG of LE and SD rats included a distinct b-wave, after potential, c-wave, fast oscillation, and a slow potential of positive polarity the characteristics of which are consistent with a light peak.

scholarly journals Curcumin regulates intracellular calcium release and inhibits oxidative stress parameters, VEGF, and caspase-3/-9 levels in human retinal pigment epithelium cells

2017 ◽  
Vol 104 (4) ◽  
pp. 301-315 ◽  
Author(s):  
H Bardak ◽  
AC Uğuz ◽  
Y Bardak
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Intracellular Calcium ◽  
Blue Light ◽  
Caspase 3 ◽  
Calcium Release ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Expression Levels

In this study, we aimed to observe whether curcumin (cur), a polyphenolic compound derived from the dietary spice turmeric, a yellow substance obtained from the root of the plant Curcuma longa Linn, has any protective effect against blue light irradiation in human retinal pigment epithelium (ARPE-19) cells. For this purpose, we evaluated the intracellular calcium release mechanism, poly ADP ribose polymerase (PARP), procaspase-3/-9 protein expression levels, caspase activation, and reactive oxygen species levels. ARPE-19 cells were divided into four main groups, such as control, cur, blue light, and cur + blue light. Results were evaluated by Kruskal–Wallis and Mann–Whitney U tests as post hoc tests. The cells in cur and cur + blue light samples were incubated with 20 μM cur. Blue light exposure was performed for 24 h in an incubator. Lipid peroxidation and cytosolic-free Ca2+ [Ca2+]i concentrations were higher in the blue light exposure samples than in the control samples; however, their levels were determined as significantly lower in the cur and cur + blue light exposure samples than in the blue light samples alone. PARP and procaspase-3 levels were significantly higher in blue light samples. Cur administration significantly decreased PARP and procaspase-3 expression levels. Reduced glutathione and glutathione peroxidase values were lower in the blue light exposure samples, although they were higher in the cur and cur + blue light exposure samples. Caspase-3 and -9 activities were lower in the cur samples than in the blue light samples. Moreover, vascular endothelial growth factor (VEGF) levels were significantly higher in the blue light exposure samples. In conclusion, cur strongly induced regulatory effects on oxidative stress, intracellular Ca2+ levels, VEGF levels, PARP expression levels, and caspase-3 and -9 values in an experimental oxidative stress model in ARPE-19 cells.

Sign in / Sign up

Export Citation Format

Share Document