Photosensitized oxidative stress to ARPE-19 cells decreases protein receptors that mediate photoreceptor outer segment phagocytosis
Open accessAbstract
PURPOSE: To determine whether previously shown photodynamic (PD)-induced inhibition of specific photoreceptor outer segment (POS) phagocytosis by ARPE-19 cells is associated with reductions in receptor proteins mediating POS phagocytosis, and if PD treatment with merocyanine-540 (MC-540) produces additional effects leading to its inhibition of nonspecific phagocytosis. METHODS: ARPE-19 cells preloaded with MC-540 or rose bengal (RB) were sublethally irradiated with green light. Phagocytosis of POS was measured by flow cytometry and POS receptor proteins (Mer tyrosine kinase receptor [MerTK] and integrin subunits αv and β5) and β-actin were quantified by Western blotting at 0.5 and 24 hours after irradiation, with comparison to samples from nonsensitized control cultures. The intact integrin heterodimer αvβ5 was quantified by immunoprecipitation followed by blotting. The distribution of N-cadherin, ZO-1, and F-actin was visualized by fluorescence microscopy. RESULTS: Mild PD stress mediated by both photosensitizers that elicits no significant morphologic changes produces transient and recoverable reductions in MerTK. The individual αv and β5 integrin subunits are also reduced but only partially recover. However, there is sufficient recovery to support full recovery of the functional heterodimer. Light stress mediated by MC-540 also reduced levels of actin, which is known to participate in the internalization of particles regardless of type. CONCLUSIONS: After PD treatment POS receptor protein abundance and phagocytosis show a coincident in time reduction then recovery suggesting that diminution in receptor proteins contributes to the phagocytic defect. The additional inhibition of nonspecific phagocytosis by MC-540-mediated stress may result from more widespread effects on cytosolic proteins. The data imply that phagocytosis receptors in RPE cells are sensitive to oxidative modification, raising the possibility that chronic oxidative stress in situ may reduce the efficiency of the RPE's role in photoreceptor turnover, thereby contributing to retinal degenerations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
ARPE-19 and primary RPE cells ingest OSs in less than 1 h.
“ARPE-19 and primary RPE cells have been shown to ingest OSs in less than 1 h (Gibbs et al., 2003; Damek-Poprawa et al., 2009; Olchawa et al., 2013; Wavre-Shapton et al., 2014)”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Olchawa et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration
Beatty, S., Koh, H.-H., Phil, M., Henson, D., & Boulton, M. (2000) · Survey of Ophthalmology · doi:10.1016/s0039-6257(00)00140-5 · Cited by 2,051 · see citing works
Klein, R., Klein, R., Moss, S. E., & Linton, K. L. P. (1992) · Ophthalmology · doi:10.1016/s0161-6420(92)32011-1 · Cited by 1,382 · see citing works
Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat
D'Cruz, P. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.4.645 · Cited by 869 · see citing works
INHERITED RETINAL DYSTROPHY IN THE RAT
Dowling, J. E., & Sidman, R. L. (1962) · The Journal of Cell Biology · doi:10.1083/jcb.14.1.73 · Cited by 804 · see citing works
Rod outer segment disk shedding in rat retina: relationship to cyclic lighting
LaVail, M. M. (1976) · Science · doi:10.1126/science.982063 · Cited by 689 · see citing works
Identification of the gene responsible for Best macular dystrophy
Petrukhin, K. E., Koisti, M. J., Bakall, B., Li, W., Xie, G., Marknell, T., Sandgren, O., Forsman, K., Holmgren, G., Andréasson, S., et al. (1998) · Nature Genetics · doi:10.1038/915 · Cited by 688 · see citing works
Oxidative Damage and Age Related Macular Degeneration
Renganathan, K. (2008) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 565 · see citing works
(1999) · PubMed · Cited by 539 · see citing works
Mullen, R. J., & LaVail, M. M. (1976) · Science · doi:10.1126/science.1265483 · Cited by 530 · see citing works
(2011) · SpringerReference · doi:10.1007/springerreference_36603 · Cited by 486 · see citing works
Mata, N. L., Weng, J., & Travis, G. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130110497 · Cited by 456 · see citing works
Blue Light-induced Reactivity of Retinal Age Pigment
Rôżanowska, M., Jarvis-Evans, J., Korytowski, W., Boulton, M. E., Burke, J. M., & Sarna, T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18825 · Cited by 426 · see citing works
Self-citationSunlight and Age-Related Macular Degeneration
Cruickshanks, K. J. (1993) · Archives of Ophthalmology · doi:10.1001/archopht.1993.01090040106042 · Cited by 401 · see citing works
Photochemical Damage of the Retina
Wu, J., Seregard, S., & Algvere, P. V. (2006) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2006.06.009 · Cited by 398 · see citing works
Sarna, T. (1992) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/1011-1344(92)85027-r · Cited by 396 · see citing works
Self-citationAge‐related maculopathy and the impact of blue light hazard
Algvere, P. V., Marshall, J., & Seregard, S. (2006) · Acta Ophthalmologica Scandinavica · doi:10.1111/j.1600-0420.2005.00627.x · Cited by 394 · see citing works
Finnemann, S. C., Bonilha, V. L., Marmorstein, A. D., & Rodriguez-Boulan, E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12932 · Cited by 382 · see citing works
The susceptibility of the retina to photochemical damage from visible light
Hunter, J. J., Morgan, J. I. W., Merigan, W. H., Sliney, D. H., Sparrow, J. R., & Williams, D. R. (2011) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.11.001 · Cited by 355 · see citing works
Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking αvβ5 integrin
Nandrot, E. F., Kim, Y., Brodie, S. E., Huang, X., Sheppard, D., & Finnemann, S. C. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041447 · Cited by 319 · see citing works
Loss of melanin from human RPE with aging: possible role of melanin photooxidation
Sarna, T., Burke, J. M., Korytowski, W., Rôżanowska, M., Skumatz, C. M. B., Zaręba, A., & Zaręba, M. (2003) · Experimental Eye Research · doi:10.1016/s0014-4835(02)00247-6 · Cited by 263 · see citing works
Self-citationOxidative Stress Affects the Junctional Integrity of Retinal Pigment Epithelial Cells
Bailey, T. A., Kanuga, N., Romero, I. A., Greenwood, J., Luthert, P. J., & Cheetham, M. E. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-0351 · Cited by 245 · see citing works
Feng, W., Yasumura, D., Matthes, M. T., LaVail, M. M., & Vollrath, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107876200 · Cited by 244 · see citing works
Essential role for MFG-E8 as ligand for αvβ5 integrin in diurnal retinal phagocytosis
Nandrot, E. F., Anand, M., Almeida, D., Atabai, K., Sheppard, D., & Finnemann, S. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704756104 · Cited by 241 · see citing works
Blue Light-Induced Singlet Oxygen Generation by Retinal Lipofuscin in Non-Polar Media
Rôżanowska, M., Wessels, J. M., Boulton, M. E., Burke, J. M., Rodgers, M. A. J., Truscott, T. G., & Sarna, T. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00395-x · Cited by 227 · see citing works
Self-citationLipofuscin is a photoinducible free radical generator
Boulton, M. E., Dontsov, A. E., Jarvis-Evans, J., Оstrovsky, М. А., & Svistunenko, D. A. (1993) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/1011-1344(93)87085-2 · Cited by 222 · see citing works
Defective ingestion of rod outer segments by cultured dystrophic rat pigment epithelial cells.
Chaitin, M. H., & Hall, M. O. (1983) · PubMed · Cited by 215 · see citing works
Hydrogen Peroxide Causes Significant Mitochondrial DNA Damage in Human RPE Cells
Ballinger, S. W., Houten, B. V., Conklin, C. A., Jin, G., & Godley, B. F. (1999) · Experimental Eye Research · doi:10.1006/exer.1998.0661 · Cited by 209 · see citing works
Focal adhesion kinase signaling promotes phagocytosis of integrin‐bound photoreceptors
Finnemann, S. C. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg416 · Cited by 208 · see citing works
The Photoreactivity of the Retinal Age Pigment Lipofuscin
Wassell, J., Davies, S., Bardsley, W. G., & Boulton, M. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.23828 · Cited by 173 · see citing works
Finnemann, S. C., & Silverstein, R. L. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.9.1289 · Cited by 154 · see citing works
Carr, A. F., Vugler, A., Lawrence, J. M., Chen, L., Ahmado, A., Chen, F. K., Semo, M., Gias, C., da Cruz, L., Moore, H. D. M., et al. (2009) · PubMed Central · Cited by 152 · see citing works
Kalyanaraman, B., Feix, J. B., Sieber, F., et al. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.9.2999 · Cited by 145 · see citing works
Epithelial phenotype and the RPE: Is the answer blowing in the Wnt?
Burke, J. M. (2008) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.08.002 · Cited by 124 · see citing works
Self-citationMerocyanine 540 as a fluorescent probe of membranes: Staining of electrically excitable cells
Easton, T. G., Valinsky, J. E., & Reich, E. (1978) · Cell · doi:10.1016/0092-8674(78)90321-5 · Cited by 110 · see citing works
Sieber, F. (1987) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1987.tb04890.x · Cited by 108 · see citing works
Sunlight and age-related macular degeneration.
West, E. S., & Schein, O. D. (2005) · PubMed · Cited by 102 · see citing works
Possible roles of microtubules and actin filaments in retinal pigmented epithelium
Burnside, M. B. (1976) · Experimental Eye Research · doi:10.1016/0014-4835(76)90208-6 · Cited by 87 · see citing works
Rose bengal radicals and their reactivity
Lambert, C., Sarna, T., & Truscott, T. G. (1990) · Journal of the Chemical Society Faraday Transactions · doi:10.1039/ft9908603879 · Cited by 78 · see citing works
Self-citationLin, H., & Clegg, D. (1998) · PubMed · Cited by 77 · see citing works
Anderson, D. H., Johnson, L. V., & Hageman, G. S. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903600102 · Cited by 65 · see citing works
Actin filaments in apical projections of the primate pigmented epithelial cell.
Burnside, B., & Laties, A. M. (1976) · PubMed · Cited by 61 · see citing works
Yu, C.-C., Nandrot, E. F., Dun, Y., & Finnemann, S. C. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.021 · Cited by 61 · see citing works
Putting, B. J., van Best, J. A., Vrensen, G. F. J. M., & Oosterhuis, J. A. (1994) · Experimental Eye Research · doi:10.1006/exer.1994.1192 · Cited by 56 · see citing works
Bcl-2 Overexpression Increases Survival in Human Retinal Pigment Epithelial Cells Exposed to H2O2
Godley, B. F., Jin, G., Guo, Y.-S., et al. (2002) · Experimental Eye Research · doi:10.1006/exer.2001.1146 · Cited by 55 · see citing works
Miceli, M. V., Newsome, D. A., & Tate, D. J. (1997) · PubMed · Cited by 52 · see citing works
Influence of dye and protein location on photosensitization of the plasma membrane
Kochevar, I. E., Bouvier, J., Lynch, M. C., et al. (1994) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(94)00236-3 · Cited by 52 · see citing works
SINGLET OXYGEN INVOLVEMENT IN PHOTOHEMOLYSIS SENSITIZED BY MEROCYANINE‐540 and ROSE BENGAL
Valenzeno, D. P., Trudgen, J., Hutzenbuhler, A., et al. (1987) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1987.tb04881.x · Cited by 49 · see citing works
Autofluorescent inclusions in long-term postconfluent cultures of retinal pigment epithelium.
Burke, J. M., & Skumatz, C. M. B. (1998) · PubMed · Cited by 41 · see citing works
Self-citationHo, T., Yang, Y., Cheng, H.-C., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.164 · Cited by 41 · see citing works
Żądło, A. C., Burke, J. M., & Sarna, T. (2009) · Photochemical & Photobiological Sciences · doi:10.1039/b901820d · Cited by 38 · see citing works
Self-citationSieber, F. (1987) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1987.tb04738.x · Cited by 33 · see citing works
αvβ5 Integrin Receptors at the Apical Surface of the RPE: One Receptor, Two Functions
Nandrot, E. F., Chang, Y., & Finnemann, S. C. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-74904-4_43 · Cited by 32 · see citing works
Roles of αvβ5, FAK and MerTK in oxidative stress inhibition of RPE cell phagocytosis
Qin, S., & Rodrigues, G. A. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.11.007 · Cited by 26 · see citing works
Putting, B. J., van Best, J. A., Zweypfenning, R. C. V. J., et al. (1993) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/bf00936526 · Cited by 23 · see citing works
Croce, A. C., Wyroba, E., & Bottiroli, G. F. (1992) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/1011-1344(92)80019-r · Cited by 22 · see citing works
The role of free radicals in photosensitized oxidation reactions induced by merocyanine 540
Sarna, T., Pilas, B., Lambert, C., et al. (1991) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/1010-6030(91)87053-x · Cited by 20 · see citing works
Self-citationSub‐lethal Photodynamic Damage to ARPE‐19 Cells Transiently Inhibits Their Phagocytic Activity†
Olchawa, M., Szewczyk, G. M., Zaręba, M., Pilat, A. K., Bzowska, M., Mikolajczyk, T. P., & Sarna, T. (2010) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2010.00727.x · Cited by 17 · see citing works
Self-citationWilliams, L. L., Lew, H. M., Shannon, B. T., Singley, C. T., Davidorf, F. H., Jin, R., & Wolinsky, J. S. (1993) · PubMed Central · Cited by 14 · see citing works
Hall, M. O., Abrams, T. A., & Burgess, B. L. (2003) · Experimental Eye Research · doi:10.1016/s0014-4835(03)00158-1 · Cited by 10 · see citing works
Endogenous N-cadherin in a subpopulation of MDCK cells: distribution and catenin complex composition
Youn, Y.-H., Hong, J., & Burke, J. M. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.09.023 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [1]1. Bok D, Young RW. Phagocytic properties of the retinal pigment epithelium. In: Zinn KM, Marmor MF. eds *The Retinal Pigment Epithelium*. Cambridge, MA: Harvard University Press; 1979: 148–174 [[Google Scholar](https://scholar.google.com/scholar_lookup?title=The%20Retinal%20Pigment%20Epithelium&author=D%20Bok&author=RW.%20Young&publication_year=1979&)] *
Cited by
Sorted by citations
The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
Understanding photoreceptor outer segment phagocytosis: use and utility of RPE cells in culture
Mazzoni, F., Safa, H., & Finnemann, S. C. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.01.010 · Cited by 221 · see citing works
Różanowska, M. B., & Różanowski, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020922 · Cited by 14 · see citing works
- Authors
- Olchawa, M. M., Herrnreiter, A. M., Skumatz, C. M. B., Zareba, M., Sarna, T. J., & Burke, J. M.
- Affiliations
- Jagiellonian University (PL)
- Medical College of Wisconsin (US)
- From the Department of Ophthalmology, Eye Institute, Medical College of Wisconsin, Milwaukee, Wisconsin; and the
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2013-03-28
- Volume
- 54
- Issue
- 3
- Pages
- 2276
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3626524
- OpenAlex
- W2036419084
- Cited by
- 23
- References
- 61
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 1 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 2
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (1c06rr016511-01a1)
- National Eye Institute (P30 EY01931, P30EY001931, R01EY019664)
- National Center for Research Resources (C06-RR016511, C06 RR-RR016511)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- photoreceptor outer segment phagocytosis, retinal pigment epithelium, ARPE-19 cells, photodynamic therapy, oxidative stress, photosensitizers, merocyanine 540, rose bengal, MERTK, integrin αvβ5, N-cadherin, ZO-1, actin, retinal degeneration
- MeSH terms
- Cell Survival, Cells, Cultured, Flow Cytometry, Humans, Phagocytosis, Photochemotherapy, Pyrimidinones, Blotting, Western, Photosensitizing Agents, Oxidative Stress, Receptor Protein-Tyrosine Kinases, Integrin alphaV, Integrin beta Chains, Retinal Photoreceptor Cell Outer Segment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
