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Cited by 73Autophagy in Disease and TherapyCellular transport and secretionRetinal Diseases and Treatments

RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye

Open access
Muniz-Feliciano, Luis, Doggett, Teresa A., Zhou, Zhenqing, Ferguson, Thomas A.·2017·Autophagy
DOI 10.1080/15548627.2017.1380124PMC PMC5788552
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Abstract

Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions. Our data reveal that RPE cells promote LAP through the expression of RUBCN/Rubicon (RUN domain and cysteine-rich domain containing Beclin 1-interacting protein) and suppress autophagy through the activation of EGFR (epidermal growth factor receptor). In the morning when photoreceptor outer segments (POS) phagocytosis and LAP are highest, RUBCN expression is increased. At the same time, outer segment phagocytosis activates the EGFR resulting in MTOR (mechanistic target of rapamycin [serine/threonine kinase]) stimulation, the accumulation of SQSTM1/p62, and the phosphorylation of BECN1 (Beclin 1, autophagy related) on an inhibitory residue thereby suppressing autophagy. Silencing Rubcn, preventing EGFR activity or directly inducing autophagy in RPE cells by starvation inhibits phagocytic degradation of POS. Thus, RPE cells regulate lysosomal pathways during the critical period of POS phagocytosis to support retinal homeostasis.

AI snapshot

Written from the paper’s full text.

TL;DR

In RPE cells, RUBCN promotes LC3-associated phagocytosis (LAP) and is required for degradation of phagocytosed photoreceptor outer segments, while EGFR activation during POS phagocytosis suppresses canonical autophagy. Starvation-induced autophagy prevents RUBCN association with POS phagosomes and impairs POS degradation, suggesting RPE cells balance LAP and autophagy.

Key findings

  • RUBCN is required for LAP and POS degradation: *Rubcn* knockdown prevented GFP-LC3 recruitment to POS phagosomes but not rapamycin-induced GFP-LC3 puncta; *Rubcn* silencing delayed POS degradation similarly to E64d/pepstatin A. Silencing LAP mediators *Atg5*, *Becn1*, or *Atg4b* also inhibited POS degradation, whereas silencing *Rb1cc1* or *Atg14* had no effect.
  • In C57BL/6J mouse RPE flat mounts, 75–80% of RHO-positive phagosomes were RUBCN-positive at 7 AM, with a significant reduction at 7 PM; RUBCN protein was higher at 7 AM than 7 PM. At 7 AM, SQSTM1 accumulated and RPS6KB1 and BECN1 Ser234 were phosphorylated, indicating suppressed autophagy.
  • Starvation/fasting for 24 h increased GFP-LC3 puncta and decreased SQSTM1 in RPE, reduced RUBCN-positive phagosomes, and increased RHO-positive phagosomes per RPE cell. In RPE-J cells, starvation reduced POS degradation at 16 h and 24 h without affecting POS binding or internalization, and reduced LAMP1/LAMP2 colocalization with engulfed POS.
  • POS phagocytosis induced EGFR phosphorylation at Tyr1068. Erlotinib blocked p-EGFR and impaired POS degradation, reduced RUBCN levels during POS phagocytosis, decreased SQSTM1, RPS6KB1 activation, and p-BECN1 Ser234; cetuximab blocked EGFR ligand binding and delayed POS degradation without altering POS binding or uptake.

Methods

  • Differentiated rat RPE-J cells were used with siRNA knockdown, GFP-LC3 transfection, labeled or unlabeled POS feeding, POS pulse-chase RHO western blotting, and confocal microscopy; starvation was induced with 0.1% FBS medium.
  • Male C57BL/6J and GFP-LC3 transgenic mice, including 16-week-old mice, were housed on a 12-h light/12-h dark cycle; RPE flat mounts and isolated RPE were analyzed at 7 AM and 7 PM, and fasting was 24 h food withdrawal.
  • Main analyses included western blotting, immunofluorescence confocal microscopy, and quantification of colocalization; statistics used two-tailed unpaired Student t tests with p<0.05, and error bars represent standard error.

Limitations

  • Stated in the paper: the possible link between stress-induced autophagy, impaired POS degradation, and AMD disease progression “will require further study”; whether EGFR engagement maintains appropriate RUBCN levels is “currently under study”; and RUBCN displacement to endosomes during starvation is presented as one possibility.
  • Evident from the text: the work relies on the rat RPE-J cell line and mouse models, with no human RPE data; some experiments are described as representative from only 2 independent experiments (e.g., Fig. 4B, Fig. 5A, Fig. 8A).
  • Evident from the text: autophagy suppression is inferred from SQSTM1 accumulation, RPS6KB1 phosphorylation, and BECN1 Ser234 phosphorylation rather than direct autophagic flux measurements.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1080/15548627.2017.1380124

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 39 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    RUBCN is required for LAP in RPE cells.

    “RUBCN is required for LAP in RPE”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] source

      Not checked in the free run.

  • Findingown data

    Rubcn knockdown does not affect expression of other known mediators of LAP (ATG5, BECN1, ATG4B) or canonical autophagy (ATG14, RB1CC1).

    “Rubcn knockdown did not affect the expression of the other known mediators of LAP (ATG5, BECN1, ATG4B) or those of the canonical autophagy pathway (ATG14, RB1CC1) (Fig. 1A).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [13] source

      Not checked in the free run.

    • cites [20] source

      Not checked in the free run.

  • Findingnone given

    In the morning, when POS phagocytosis and LAP are highest, RUBCN expression is increased.

    “In the morning when photoreceptor outer segments (POS) phagocytosis and LAP are highest, RUBCN expression is increased.”
    Quote in the paperSubstantial claim
  • Findingown data

    Gene silencing had no effect on the number of bound or internalized POS by RPE-J cells.

    “Gene silencing (confirmed by western blotting, Fig. S3A-E) had no effect on the number of bound or internalized POS by the RPE-J cells (Fig. S3F-G).”
    Quote in the paperSubstantial claim
  • Findingown data

    Mouse RPE cells showed phosphorylation of BECN1 at Ser234 at 7 AM.

    “as well as phosphorylation of BECN1 (p-BECN1) at its Ser234 residue (Fig. 3D).”
    Quote in the paperSubstantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 6

  • May combine two claims.

    Findingown data

    SQSTM1 was significantly decreased at 7 PM compared to 7 AM in mouse RPE, suggesting POS phagocytosis might affect the autophagy pathway.

    “However, we noted a significant decrease in SQSTM1 at 7 PM compared to 7 AM suggesting that POS phagocytosis might affect the autophagy pathway.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Knockdown of Rubcn prevents POS-induced LAP but does not affect GFP-LC3 puncta formation during canonical autophagy induced by rapamycin.

    “Knockdown of Rubcn prevented POS-induced LAP (Fig. 1B, arrowheads, inset) but did not affect GFP-LC3 C puncta formation during canonical autophagy induced by rapamycin (Fig. 1B, bottom panels).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [13] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Erlotinib did not affect RUBCN expression under basal conditions but reduced RUBCN levels during POS phagocytosis.

    “Interestingly, whereas erlotinib did not affect the expression levels of RUBCN under basal conditions (RPE-J cells incubated without POS), it did reduce the levels of the protein during POS phagocytosis (Fig. 7A; 1, 3, and 6 h).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Starvation-induced autophagy prevented association of RUBCN with the phagosome and impaired POS degradation.

    “Thus, while it was previously shown that the induction of autophagy with rapamycin did not affect the formation of GFP-LC3 C phagosomes 12,13 ; these new data reveal that starvation-induced autophagy prevented association of RUBCN with the phagosome and impaired POS degradation.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [13] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Knockdown of Rubcn does not affect the number of lysosomes but significantly reduces the percentage of LAMP1- and LAMP2-positive phagosomes.

    “However, whereas knockdown of Rubcn did not affect the number of lysosomes (as detected in Fig. 2G-H; or by expression of LAMP1 or LAMP2 protein, see Fig. S2A-B), it significantly reduced the percentage of LAMP1-and LAMP2-positive phagosomes (Fig. 2G-H, arrowheads, bar graphs), confirming the importance of RUBCN for POS degradation via the lysosomal pathway.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under serum withdrawal, RUBCN did not associate with POS-containing phagosomes, whereas in complete medium the majority of POS colocalized with RUBCN.

    “Interestingly, while the majority of POS (red) in complete medium colocalized with RUBCN (green) (Fig. 5D, left micrograph, arrows, inset), RUBCN did not associate with the POS-containing phagosomes under serum withdrawal (Fig. 5D, right panel, arrowheads, inset).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In RPE-J cells fed unlabeled POS, starvation significantly reduced degradation as indicated by accumulation of RHO at 16 h and 24 h, without affecting the number of bound or internalized outer segments at 6 h.

    “When RPE-J cells were fed unlabeled POS, starvation significantly reduced degradation as indicated by the accumulation of RHO measured at 16 h and 24 h (Fig. 5B), without affecting the number of bound or internalized outer segments at 6 h after initial POS feeding (Fig. 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fasting for 24 h significantly enhanced GFP-LC3 puncta and decreased SQSTM1 in RPE, suggesting fasting induced autophagy in the RPE.

    “Under fed conditions, GFP-LC3 was diffuse throughout the cytoplasm (Fig. 4A, Left panel); however, following 24 h of fasting GFP-LC3 puncta were significantly enhanced (Fig. 4A, right panel, arrows) and we simultaneously observed decreased SQSTM1 (Fig. 4B) further suggesting that fasting mice induced autophagy in the RPE.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Silencing Rubcn, preventing EGFR activity, or directly inducing autophagy in RPE cells by starvation inhibits phagocytic degradation of POS.

    “Silencing Rubcn, preventing EGFR activity or directly inducing autophagy in RPE cells by starvation inhibits phagocytic degradation of POS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Erlotinib treatment had no effect on the number of bound or internalized POS but impaired the ability of RPE-J cells to degrade POS.

    “Erlotinib treatment had no effect on the number of bound or internalized POS by the RPE-J cells (Fig. 6C), but importantly, erlotinib treatment impaired the ability of RPE-J cells to degrade POS (Fig. 6D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fasting did not affect RUBCN expression but reduced the number of RUBCN+ phagosomes in freshly prepared mouse RPE flat mounts compared to fed mice.

    “When we examined the effect of fasting on RUBCN, we observed that while fasting did not affect RUBCN expression (Fig. 4B) it reduced the number of RUBCN C phagosomes in freshly prepared mouse RPE flat mounts (Fig. 4C, right panel, arrowheads) compared to RPE cells from fed mice (Fig. 4C, left panel, arrows).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Silencing Atg5, Becn1, or Atg4b inhibits POS degradation, while inhibiting Rb1cc1 or Atg14 has no effect.

    “Silencing the expression of known mediators of LAP (Atg5, Becn1, Atg4b) (Fig. 2B-D) also inhibited POS degradation while inhibiting Rb1cc1 of the autophagy preinitiation complex (ATG13-ULK1-RB1CC1-ATG101) or the essential autophagy gene Atg14 had no effect (Fig. 2E-F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fasting increased the number of RHO+ phagosomes per mouse RPE cell, suggesting degradation of POS was impaired.

    “In addition, fasting increased the number of RHO C phagosomes per mouse RPE cell (Fig. 4D) suggesting that degradation of the POS was impaired.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RUBCN is constitutively expressed in RPE cells both in vivo and in vitro and is recruited to the POS-containing phagosome.

    “We found that RUBCN was constitutively expressed in RPE cells both in vivo and in vitro and was similarly recruited to the POScontaining phagosome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Inhibition of EGFR signaling with erlotinib suppressed POS degradation and activated autophagy.

    “Importantly, inhibition of EGFR signaling with the tyrosine kinase inhibitor erlotinib suppressed POS degradation and activated autophagy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RUBCN recruitment is necessary for delivery of LAMP1- and LAMP2-positive lysosomes and for POS degradation.

    “RUBCN recruitment was necessary for delivery of the LAMP1-and LAMP2-positive lysosomes (Fig. 2), in a manner similar to macrophages, 20 and was necessary for POS degradation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    POS phagocytosis did not induce RUBCN protein, suggesting that simply modulating RUBCN levels cannot account for the findings.

    “However, POS phagocytosis did not induce RUBCN protein (Fig. 7B) suggesting that simply modulating RUBCN levels cannot account for our findings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cetuximab prevented EGFR activation by EGF and delayed degradation of POS in RPE-J cells, while not altering binding or uptake of POS.

    “Cetuximab prevented EGFR activation by EGF (Fig. 8A) and also delayed degradation of POS in RPE-J cells (Fig. 8B), while not altering binding or uptake of POS by RPE-J (Fig. 8C).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Erlotinib treatment decreased SQSTM1 levels, RPS6KB1 activation, and p-BECN1 at Ser234 in RPE-J cells fed POS, indicating upregulation of autophagy when p-EGFR was inhibited.

    “Furthermore, erlotinib treatment decreased SQSTM1 levels, RPS6KB1 activation, and p-BECN1 at Ser234 in RPE-J cells fed POS (Fig. 7A) indicating the upregulation of autophagy when p-EGFR was inhibited.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Inhibition of EGFR with erlotinib prevented RUBCN association with the POS-containing phagosome, thereby compromising POS degradation.

    “Inhibition of EGFR with this compound also prevented RUBCN association with the POS-containing phagosome thereby compromising POS degradation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Starvation did not affect RUBCN protein levels but prevented association of RUBCN with RHO+ phagosomes, a necessary step for degradation of outer segments.

    “Whereas starvation did not affect the levels of the RUBCN protein, it prevented association of RUBCN with the RHO C phagosomes, a necessary step for the degradation of the outer segments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Outer segment phagocytosis activates EGFR, resulting in MTOR stimulation, accumulation of SQSTM1/p62, and phosphorylation of BECN1 on an inhibitory residue, thereby suppressing autophagy.

    “At the same time, outer segment phagocytosis activates the EGFR resulting in MTOR (mechanistic target of rapamycin [serine/threonine kinase]) stimulation, the accumulation of SQSTM1/p62, and the phosphorylation of BECN1 (Beclin 1, autophagy related) on an inhibitory residue thereby suppressing autophagy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    RPE cells promote LAP through the expression of RUBCN and suppress autophagy through the activation of EGFR.

    “Our data reveal that RPE cells promote LAP through the expression of RUBCN/Rubicon (RUN domain and cysteinerich domain containing Beclin 1-interacting protein) and suppress autophagy through the activation of EGFR (epidermal growth factor receptor).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    While RPE suppress autophagy during phagocytosis, during periods of cellular stress they refocus their resources on cell survival at the expense of POS degradation.

    “These results support the idea that while RPE suppress autophagy during phagocytosis, during periods of cellular stress they refocus their resources on cell survival at the expense of POS degradation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Hallmarks of suppressed autophagy indicate that LAP and autophagy may be competing for resources and might not easily co-exist in RPE cells.

    “These hallmarks of suppressed autophagy 11,31,32 indicate that LAP and autophagy may be competing for resources and might not easily co-exist in RPE cells.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [11] source

      Not checked in the free run.

    • cites [31] source

      Not checked in the free run.

    • cites [32] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MTOR activation is an indicator of suppressed autophagy, as is p-BECN1 at Ser234 where it is targeted by AKT1 during MTOR activation.

    “MTOR activation is an indicator of suppressed autophagy 31 as is p-BECN1 at this Ser234 residue where it is targeted by the serine/threonine kinase AKT1 during MTOR activation.32”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [31] source

      Not checked in the free run.

    • cites [32] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    RUBCN is an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.

    “Interestingly, while RUBCN is a LAP-specific mediator, it is also an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.21,22”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] source

      Not checked in the free run.

    • cites [22] source

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  • May combine two claims.

    Premisecitation

    Photoreceptor tip shedding is maximal in the morning just after onset of the light cycle, linking the process to circadian rhythms.

    “Photoreceptor tip shedding occurs throughout the day, but it is maximal in the morning just after the onset of the light cycle, [8][9][10] linking the process to circadian rhythms.41,51”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [8][9][10]

      Not checked in the free run.

    • cites [41] source

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    • cites [51] source

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  • Classified as probably not a substantial claim.

    Premisecitation

    Cetuximab specifically blocks the EGFR ligand-binding domain.

    “Cetuximab, a blocker of EGFR ligand-binding.40”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All mice are free of the rd8 mutation as confirmed by PCR analysis.

    “All mice are free of the rd8 mutation 65 as confirmed by PCR analysis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All experiments contained at least 3 mice per group and were repeated a minimum of 3 times.

    “All experiments contained at least 3 mice per group and were repeated a minimum of 3 times.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All animal experiments were approved by IACUC and carried out in accordance with the ARVO Resolution on the Use of Animals for Ophthalmologic Research.

    “All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at Washington University School of Medicine, and were carried out in strict accordance with the ARVO Resolution on the Use of Animals for Ophthalmologic Research.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    p-EGFR at Tyr1068 is a major autophosphorylation site of the receptor.

    “a major autophosphorylation site of the receptor.36”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] source

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    The siRNA oligonucleotides used to silence Rubcn, Atg5, Becn1, Atg4b, Atg14, and Rb1cc1 are specific and do not produce off-target effects that affect the measured pathways.

    “Following successful knockdown of Rubcn in RPE-J cells by siRNA oligonucleotides (Fig. 1A)”
    “Gene silencing (confirmed by western blotting, Fig. S3A-E) had no effect on the number of bound or internalized POS by the RPE-J cells (Fig. S3F-G).”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The kinetics of OS uptake and OS phagosome degradation are sensitive to the state of RPE differentiation.

    “Although some studies on LAP in the RPE have been performed with undifferentiated RPE-J cells (Kim et al., 2013; Muniz-Feliciano et al., 2017), it is well-established that the kinetics of OS uptake and OS phagosome degradation are sensitive to the state of RPE differentiation.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Muniz-Feliciano et al., 2017

  • Loss of Rubicon decreased OS degradation in RPE-J cells.

    “Loss of Rubicon decreased OS degradation; however, these RPE-J cells also showed a dramatic loss of LAMP1-labeled lysosomes (Muniz-Feliciano et al., 2017), suggesting that knocking out Rubicon could delay OS clearance by interfering with multiple pathways including endosome maturation.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Muniz-Feliciano et al., 2017

  • Rubicon levels in the RPE are elevated at light onset.

    “The observation that Rubicon levels in the RPE are elevated at light onset (Muniz-Feliciano et al., 2017) suggests that synchronized OS phagocytosis is required for Rubicon activation.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Muniz-Feliciano et al., 2017

  • The elevation of Rubicon levels in the RPE at light onset suggests that synchronized OS phagocytosis is required for Rubicon activation.

    “The observation that Rubicon levels in the RPE are elevated at light onset (Muniz-Feliciano et al., 2017) suggests that synchronized OS phagocytosis is required for Rubicon activation.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Muniz-Feliciano et al., 2017

  • RPE-J cells with loss of Rubicon also showed a dramatic loss of LAMP1-labeled lysosomes.

    “Loss of Rubicon decreased OS degradation; however, these RPE-J cells also showed a dramatic loss of LAMP1-labeled lysosomes (Muniz-Feliciano et al., 2017), suggesting that knocking out Rubicon could delay OS clearance by interfering with multiple pathways including endosome maturation.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Muniz-Feliciano et al., 2017

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 4D is described using different outcome measures

    Minor

    The results describe Figure 4D as showing the number of phagosomes per RPE cell, whereas its caption says the quantified outcome was the percentage of RPE cells with phagosomes. These are different measures.

1 of 1

The citation lists haven’t been fetched yet

References 68 · Cited by 73

Research works printed but not linked: 1

  1. Naash MI, 1997, Invest Ophthal Vis Sci, 38, 2344

Authors
Muniz-Feliciano, L., Doggett, T. A., Zhou, Z., & Ferguson, T. A.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Ferguson, Thomas A.
ORCID
Muniz-Feliciano, Luis
Venue
Autophagy
Publisher
Informa UK Limited
Published
2017-12-02
Volume
13
Issue
12
Pages
2072-2085
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.1080/15548627.2017.1380124
PMC
PMC5788552
OpenAlex
W2757416005
Semantic Scholar
13a25f8d91c269833ca04910d9091a38b7700c46
Cited by
73
References
68
Citations by year
2026: 4 · 2025: 9 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 7
FWCI
4.92
Type
journal article
Language
en
Open access
Locations
  • Autophagy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Research to Prevent Blindness (EY02687)
  • National Eye Institute (P30EY002687, T32EY013360)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
Rubicon, EGFR, retinal pigment epithelium, LC3-associated phagocytosis, photoreceptor outer segment phagocytosis, lysosomal degradation, mTOR signaling, p62, Beclin-1, retinal homeostasis
MeSH terms
Animals, Autophagy, Ligands, Lysosomes, Male, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Phagocytosis, Phagosomes, Intracellular Signaling Peptides and Proteins, Retinal Pigment Epithelium, Retinal Photoreceptor Cell Outer Segment, ErbB Receptors

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