scholarly journals Phagocytosis of outer segments by retinal pigment epithelium: phagosome-lysosome interaction.

1993 ◽  
Vol 41 (2) ◽  
pp. 253-263 ◽  
Author(s):  
E Bosch ◽  
J Horwitz ◽  
D Bok
Keyword(s):  
Freeze Drying ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Light Cycle ◽  
Light Onset ◽  
Electron Microscopic ◽  
Electron Microscopic Immunocytochemistry ◽  
Photoreceptor Outer Segment ◽  
Outer Segments ◽  
Pigmented Epithelium

We studied phagocytosis of rod outer segments (ROS) by the retinal pigmented epithelium (RPE) using rapid freezing, freeze-drying, and electron microscopic immunocytochemistry. Phagocytosis of photoreceptor outer segment tips by the RPE occurs daily, and in rats the shedding of these tips is light-entrained to a circadian rhythm. We studied the phagocytic process 5, 30, 90, and 150 min after light onset or after subjective light onset in rats entrained to a 12-hr dark-12-hr light cycle. Lysosomes were labeled with antibodies to cathepsin D, a major lysosomal enzyme responsible for opsin degradation. Phagosomes and phagolysosomes were recognized because of the lamellar structure of their photoreceptor-derived contents. We found a population of lysosomes that fuse with one another before they interact with phagosomes. This fusion can be triggered either by light or by endogenous circadian mechanisms. We also found that lysosome-phagosome interaction occurs after the ingestion stage is completed and that this interaction occurs in two steps. First, smaller lysosomes fuse with phagosomes. Subsequently, larger lysosomes appear to interact with phagosomes via pore-like or bridge-like structures. It is proposed that interchange of contents takes place through these structures.

The rhodopsin cycle is preserved in IRBP “knockout” mice despite abnormalities in retinal structure and function

2000 ◽  
Vol 17 (1) ◽  
pp. 97-105 ◽  
Author(s):  
HARRIS RIPPS ◽  
NEAL S. PEACHEY ◽  
XIAOPING XU ◽  
SUSAN E. NOZELL ◽  
SYLVIA B. SMITH ◽  
...  
Keyword(s):  
Binding Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Indirect Evidence ◽  
Significant Loss ◽  
Subretinal Space ◽  
Electron Microscopic ◽  
Outer Segments ◽  
Structural And Functional Properties

In the vertebrate retina, vision is initiated and maintained by the photolysis and regeneration, respectively, of light-sensitive pigments in the disk membranes of the photoreceptor outer segments. This cyclical process depends on an exchange of retinoids between the photoreceptors and the retinal pigment epithelium (RPE). There is a great deal of indirect evidence that the transport of retinoids between these cellular compartments is mediated by the interphotoreceptor retinoid-binding protein (IRBP), a large glycoprotein synthesized in the photoreceptors and extruded into the interphotoreceptor matrix (IPM) that fills the subretinal space. Nevertheless, a number of in vitro experiments have demonstrated that an intermembranous transfer of retinoids can occur through an aqueous medium independent of any retinoid-binding protein. This led to the suggestion that IRBP may play the more passive role of an extracellular buffer, serving to prevent the degradation and potentially cytotoxic effects of free retinoids when large amounts are released into the IPM. We have studied the structural and functional properties of transgenic mice in which homologous recombination was used to delete the IRBP gene. Light- and electron-microscopic examination of the retinas of “knockout” (IRBP−/−) mice revealed a significant loss of photoreceptor nuclei, and profound changes in the structure and organization of the receptor outer segments. Consistent with these observations, electroretinographic recordings showed a marked reduction in response amplitude for both rod- and cone-mediated potentials. However, despite the histological and electrophysiological changes, there was no evidence of gross abnormalities in the visual cycle. After bleaching a significant fraction of the available rhodopsin, electroretinogram amplitude and rhodopsin density gradually increased toward their pre-bleach levels, and the rates of recovery were even more rapid than those seen in wild-type (IRBP+/+) mice.

scholarly journals Kif17 phosphorylation regulates its ciliary localization and photoreceptor outer segment turnover

2018 ◽  
Author(s):  
Tylor R. Lewis ◽  
Sean R. Kundinger ◽  
Brian A. Link ◽  
Christine Insinna ◽  
Joseph C. Besharse
Keyword(s):  
Mammalian Cells ◽  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Consensus Sequence ◽  
Intraflagellar Transport ◽  
Photoreceptor Outer Segment ◽  
Transgenic Expression ◽  
Outer Segments ◽  
Ciliary Localization

AbstractBackgroundKIF17, a kinesin-2 motor that functions in intraflagellar transport, can regulate the onset of photoreceptor outer segment development. However, the function of KIF17 in a mature photoreceptor remains unclear. Additionally, the ciliary localization of KIF17 is regulated by a C-terminal consensus sequence (KRKK) that is immediately adjacent to a conserved residue (mouse S1029/zebrafish S815) previously shown to be phosphorylated by CaMKII. Yet, whether this phosphorylation can regulate the localization, and thus function, of KIF17 in ciliary photoreceptors remains unknown.ResultsUsing transgenic expression in both mammalian cells and zebrafish photoreceptors, we show that phospho-mimetic KIF17 has enhanced localization to cilia. Importantly, expression of phospho-mimetic KIF17 is associated with greatly enhanced turnover of the photoreceptor outer segment through disc shedding in a cell-autonomous manner, while genetic mutants of kif17 in zebrafish and mice have diminished disc shedding. Lastly, cone expression of constitutively active tCaMKII leads to a kif17-dependent increase in disc shedding.ConclusionsTaken together, our data support a model in which phosphorylation of KIF17 promotes its ciliary localization. In cone photoreceptor outer segments, this promotes disc shedding, a process essential for photoreceptor maintenance and homeostasis. While disc shedding has been predominantly studied in the context of the mechanisms underlying phagocytosis of outer segments by the retinal pigment epithelium, this work implicates photoreceptor-derived signaling in the underlying mechanisms of disc shedding.

scholarly journals Peroxisome turnover and diurnal modulation of antioxidant activity in retinal pigment epithelia utilizes microtubule-associated protein 1 light chain 3B (LC3B)

2019 ◽  
Vol 317 (6) ◽  
pp. C1194-C1204 ◽  
Author(s):  
Lauren L. Daniele ◽  
Jennifer Caughey ◽  
Stefanie Volland ◽  
Rachel C. Sharp ◽  
Anuradha Dhingra ◽  
...  
Keyword(s):  
Light Chain ◽  
Catalase Activity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Enzyme Regulation ◽  
Immunoblot Analysis ◽  
Light Onset ◽  
Photoreceptor Outer Segment ◽  
Accumulation Of Lipids ◽  
Catalase Protein

The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid cycle, nutrient supply, ion exchange, and waste removal. Each day the RPE removes the oldest ~10% of photoreceptor outer segment (OS) disk membranes through phagocytic uptake, which peaks following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation, and cell death. OSs are rich in very long chain fatty acids, which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblot analysis, and catalase activity assays, we investigated peroxisome abundance and activity at 6 AM, 7 AM (light onset), 8 AM, and 3 PM, in wild-type (WT) mice and mice lacking microtubule-associated protein 1 light chain 3B ( Lc3b), which have impaired phagosome degradation. We found that catalase activity, but not the amount of catalase protein, is 50% higher in the morning compared with 3 PM, in RPE of WT, but not Lc3b−/−, mice. Surprisingly, we found that peroxisome abundance was stable during the day in RPE of WT mice; however, numbers were elevated overall in Lc3b−/− mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS.

A Bibliometric Analysis of the Top 100 Cited Papers in Retinal Detachment

2021 ◽  
pp. 247412642110073
Author(s):  
Masumi George Asahi ◽  
Haig Pakhchanian ◽  
Christine Doepker ◽  
Rahul Raiker ◽  
Ron P. Gallemore
Keyword(s):  
Retinal Detachment ◽  
Bibliometric Analysis ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Microscopic Analysis ◽  
The United States ◽  
Electron Microscopic ◽  
Research Areas ◽  
Science Index ◽  
Funding Agencies

Purpose: This work aimed to identify and analyze the most frequently cited articles in retinal detachment (RD). Methods: Institute for Scientific Information’s Web of Science index (Thomas Scientific) was used to identify the top 100 most cited articles on RD between 1900 and 2019. Data from the top 100 most cited articles that met inclusion criteria were analyzed based on title, citation frequency, authorship, institution, journal, year of publication, and country of origin. Results: The top 100 articles in RD were cited 88 to 480 times. Steven K. Fisher was the most cited individual, with the University of California system being the most cited organization. Sixty-four percent of the top 100 articles originated from the United States and were published in the American Journal of Ophthalmology, Ophthalmology, and Archives of Ophthalmology at frequencies of 36%, 24%, and 11%, respectively. The top funding agencies included the US Department of Health and Human Services, the National Institutes of Health, and the National Eye Institute at 29%, 28%, and 27%, respectively. The top-cited article, which assessed the role of the retinal pigment epithelium by histologic and electron microscopic analysis of RDs in eyes of owl monkeys, was by Machemer and Laqua in the American Journal of Ophthalmology. Conclusions: This bibliometric analysis provides researchers and clinicians with a detailed overview of the most cited manuscripts in RD. Such analyses may guide researchers and funding agencies on important research areas in the field.

scholarly journals Phagocytosis of Retinal Rod and Cone Photoreceptors

Physiology ◽  
2010 ◽  
Vol 25 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Brian M. Kevany ◽  
Krzysztof Palczewski
Keyword(s):  
Outer Segment ◽  
Photoreceptor Cell ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Constant Length ◽  
Outer Segments ◽  
Retinal Rod ◽  
Rod And Cone Photoreceptors

Photoreceptor cells maintain a roughly constant length by continuously generating new outer segments from their base while simultaneously releasing mature outer segments engulfed by the retinal pigment epithelium (RPE). Thus postmitotic RPE cells phagocytose an immense amount of material over a lifetime, disposing of photoreceptor cell waste while retaining useful content. This review focuses on current knowledge of outer segment phagocytosis, discussing the steps involved along with their critical participants as well as how various perturbations in outer segment (OS) disposal can lead to retinopathies.

scholarly journals Light-induced Oxidation of Photoreceptor Outer Segment Phospholipids Generates Ligands for CD36-mediated Phagocytosis by Retinal Pigment Epithelium

2006 ◽  
Vol 281 (7) ◽  
pp. 4222-4230 ◽  
Author(s):  
Mingjiang Sun ◽  
Silvia C. Finnemann ◽  
Maria Febbraio ◽  
Lian Shan ◽  
Suresh P. Annangudi ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Outer Segment

The effects of intravitreally injected bevacizumab on the retina and retina pigment epithelium: experimental in-vivo electron microscopic study in intact versus vitrectomized eyes

Open Medicine ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Nilufer Kocak ◽  
Candan Ozogul ◽  
Suleyman Kaynak ◽  
Ulker Sonmez ◽  
Mehmet Zengin ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Intravitreal Bevacizumab ◽  
Electron Microscopic Examination ◽  
Photoreceptor Cells ◽  
Control Group ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Electron Microscopes

AbstractTo analyze the retinal toxicity of bevacizumab at various doses both in vitrectomized and non-vitrectomized rabbit models. Twenty- eight rabbits were included in the study. Twenty- four rabbits were assigned to six groups, with 4 of the rabbits in the control group. The animals in Groups 1, 2 and 3 received bevacizumab at a dose of 0.3 mg, 0.5 mg and 1.5 mg /eye, respectively. The rabbits in Groups 4, 5 and 6 received intravitreal bevacizumab of 0.3 mg, 0.5 mg and 1.5mg/eye, respectively, after gas compression vitrectomy. Two weeks after the procedure, the rabbits were euthanized. Retina tissue samples were then obtained and examined with both light and electron microscopes. In Groups 1, 2 and 3 after bevacizumab injection, toxic degeneration in the photoreceptor and retinal pigment epithelium cells was observed via electron microscopic examination. The findings in Groups 4 and 5 were normal as compared to the control group. In Group 6, toxicity in the bipolar neurons and photoreceptor cells was noticed. Increased toxicity and retinal penetration were noticed in all administered doses of bevacizumab in the presence of vitreous. In addition, ocular toxicity occurred through the injection of the highest dose of bevacizumab after vitrectomy. It is possible that the bevacizumab dose and the, vitreous are as important as the drug half-life in the vitreous.

scholarly journals Macrophage and Retinal Pigment Epithelium Phagocytosis

1999 ◽  
Vol 190 (6) ◽  
pp. 861-874 ◽  
Author(s):  
Silvia C. Finnemann ◽  
Enrique Rodriguez-Boulan
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Insoluble Fraction ◽  
Αvβ3 Integrin ◽  
Apoptotic Cells ◽  
Integrin Receptor ◽  
Photoreceptor Outer Segment ◽  
Particle Binding ◽  
Pkc Activation

Noninflammatory monocyte macrophages use αvβ3 integrin to selectively bind apoptotic cells, initiating their phagocytic removal. In a related process, the retinal pigment epithelium (RPE) employs αvβ5 integrin to recognize spent photoreceptor outer segment particles (OS). Here, we show that apoptotic cells and OS compete for binding to these receptors, indicating that OS and apoptotic cells expose surface signals recognizable by αvβ3 and αvβ5. Particle binding to αvβ5 required protein kinase C (PKC) activation. In RPE, αvβ5 binding was maximally activated even before any phagocytic challenge and was reduced by PKC inhibitors. In macrophages, it was dormant but became activated upon PKC stimulation. PKC-activated αvβ5-mediated binding in macrophages differed from constitutive binding to the same integrin receptor in RPE cells in that the former followed much faster kinetics, similar to particle binding mediated by αvβ3. Activation of αvβ5 for particle binding correlated with its recruitment into a detergent-insoluble fraction, a process sensitive to pharmacological modulation of PKC in both types of phagocytes. Furthermore, αvβ5 but not αvβ3 particle binding required actin microfilaments. These data constitute the first evidence that noninflammatory phagocytes actively regulate the earliest phase of phagocytic clearance, particle binding, by controlling receptor activity.

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