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Phagocytosis of outer segments by retinal pigment epithelium: phagosome-lysosome interaction
Open accessAbstract
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.
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“‘Bridge-like structures’ were described between phagosomes and organelles thought to be lysosomes in the rat RPE as early as 30 min after light onset (Bosch et al., 1993).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Bosch et al., 1993
In the citing paper
“Indeed, we observed that in RPE-J cells engulfed POS co-localized with LAMP1, LAMP2, and cathepsin D (Figure 5A, left panels, arrows) indicating that POS degradation was proceeding (Bosch et al., 1993; Rakoczy et al., 1997; Ramkumar et al., 2010).”
From Noncanonical autophagy promotes the visual cycle (2013) · cites this paper as Bosch et al., 1993
In the citing paper
“In normal RPE cells POS were contained in single membrane phagosomes as reported (Bosch et al., 1993; Gordiyenko et al., 2010; Strauss, 2005).”
From Noncanonical autophagy promotes the visual cycle (2013) · cites this paper as Bosch et al., 1993
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Items 101–148 of 148
Müller Cells and the Retinal Pigment Epithelium
Gullapalli, V. K., Sugino, I. K., & Zarbin, M. A. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-0016-7.50128-4 · Cited by 13
Rod Outer Segment Renewal in the Retinae of Deep-sea Fish
Fröhlich, E., & Wagner, H. (1996) · Vision Research · doi:10.1016/0042-6989(96)00025-9 · Cited by 13
Al‐Bari, M. A. A., Shinohara, M., Nagai, Y., & Takayanagi, H. (2012) · Inflammation and Regeneration · doi:10.2492/inflammregen.32.222 · Cited by 12
Microtubule Motor Transport of Organelles in a Specialized Epithelium: The RPE
Hazim, R. A., & Williams, D. S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.852468 · Cited by 10
Voisin, A., Gaillard, A., Balbous, A., & Leveziel, N. (2022) · Antioxidants · doi:10.3390/antiox11040713 · Cited by 11
“Lysosomal activity is required for the digestion of photoreceptor outer segments (POS), the last stage of RPE phagocytosis [15,16].”
BackgroundAlbert, R., Kristóf, E., Zahuczky, G., Szatmári-Tóth, M., Veréb, Z., Oláh, B., Moe, M. C., Facskó, A., Fésüs, L., & Petrovski, G. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.10.026 · Cited by 11
Tamada, Y., Walkup, R. D., Shearer, T., & Azuma, M. (2007) · Current Eye Research · doi:10.1080/02713680701359633 · Cited by 9
Cell Culture Analysis of the Phagocytosis of Photoreceptor Outer Segments by Primary Mouse RPE Cells
Hazim, R. A., & Williams, D. S. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7720-8_4 · Cited by 11
“Once internalized, the POS phagosomes travel on molecular motors bound to cytoskeletal elements, including actin filaments and microtubules [7, 8], which mediate their fusion with degradative organelles such as endosomes and lysosomes [9, 10].”
BackgroundAnalysis of the Rate of Disk Membrane Digestion by Cultured RPE Cells
Diemer, T., Gibbs, D., & Williams, D. S. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-74904-4_37 · Cited by 11
Udry, F., Decembrini, S., Gamm, D. M., Déglon, N., Kostic, C., & Arsenijévic, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-65657-y · Cited by 10
Pan, H.-Y., & Valapala, M. (2021) · Cells · doi:10.3390/cells10102504 · Cited by 10
“Acidification of the phagosome is also important for its proper degradation [8].”
BackgroundKim, H.-L., Nam, S. M., Chang, B., Nahm, S., & Lee, J. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2508-9 · Cited by 10
“RPE cells daily phagocytose the tips of POS for the maintenance of the photoreceptors [24, 32].”
BackgroundResultLoss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium
FROST, L. S., LOPES, V. S., STEFANO, F. P., BRAGIN, A., WILLIAMS, D. S., MITCHELL, C. H., & BOESZE-BATTAGLIA, K. (2013) · Visual Neuroscience · doi:10.1017/s0952523813000096 · Cited by 9
“For double-labeling in immune-electron microscopy, we used a polyclonal Cat-D antibody from Dr. Dean Bok (Bosch et al., 1993 ) and mouse mAb anti-MREG 165 (Boesze-Battaglia et al., 2007 ).”
MethodPhotoreceptor—RPE Interactions
Finnemann, S. C., & Chang, Y. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-374-5_4 · Cited by 9
Jia, X., Zhao, C., Chen, Q., Du, Y., Huang, L., Ye, Z., Ren, X., Wang, S., Lee, C., Tang, Z., et al. (2017) · Thrombosis and Haemostasis · doi:10.1160/th16-11-0885 · Cited by 9
“RPE transports nutrients to and recycles wastes from photoreceptor cells to maintain function of the retina (14, 15).”
BackgroundRetinal pigment epithelium: lysosomal enzymes and aging.
Berman, E. R. (1994) · British Journal of Ophthalmology · doi:10.1136/bjo.78.2.82 · Cited by 9
Rhythmicity of the Retinal Pigment Epithelium
Ruggiero, L., & Finnemann, S. C. (2013) · Springer eBooks · doi:10.1007/978-1-4614-9613-7_6 · Cited by 9
Progranulin increases phagocytosis by retinal pigment epithelial cells in culture
Murase, H., Tsuruma, K., Kuse, Y., Shimazawa, M., & Hara, H. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24081 · Cited by 7
“The later phagocytosis step is composed of formation of the phagosomes and the fusion with a lysosome followed by digestion of ingested outer segments (Bosch et al., 1993).”
BackgroundSayama, A., Okado, K., Yamaguchi, M., Samata, N., Imaoka, M., Kai, K., & Mori, K. (2020) · Toxicologic Pathology · doi:10.1177/0192623320931415 · Cited by 7
“Increased multilamellar bodies were mainly distributed from the apical cell surface to the perinuclear zone of the RPE.”
BackgroundInfluentialLive-Cell Imaging of Phagosome Motility in Primary Mouse RPE Cells
Hazim, R. A., Jiang, M., Esteve-Rudd, J., Diemer, T., Lopes, V. S., & Williams, D. S. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-17121-0_100 · Cited by 7
“…M anuscript A uthor M anuscript A uthor M anuscript move from the apical region of the RPE towards the basal region (Herman and Steinberg 1982; Gibbs et al. 2003), fusing with degradative organelles such as endosomes and lysosomes along the way (Wavre-Shapton et al. 2014; Bosch et al. 1993).”
BackgroundMüller, C., & Finnemann, S. C. (2020) · Springer eBooks · doi:10.1007/978-3-030-28384-1_3 · Cited by 7
Sánchez, A. G., Colucci, P., Moran, A. L., López, A. M., Colligris, B., Álvarez, Y., & Kennedy, B. N. (2023) · Open Research Europe · doi:10.12688/openreseurope.15491.2 · Cited by 6
“The lysosomal activity of cathepsin D is required for the degradation of the removed OS tip, the final stage of OS phagocytosis 78 .”
Modeling of in vivo acousto-optic two-photon imaging of the retina in the human eye
Kusnyerik, Á., Rózsa, B. J., Veress, M., et al. (2015) · Optics Express · doi:10.1364/oe.23.023436 · Cited by 5
Lee, H., Hoang, A. T. N., & Lee, S.-J. (2022) · PLoS ONE · doi:10.1371/journal.pone.0274763 · Cited by 4
“The RPE protects the POS by clearing shed debris from rods and cones [8].”
BackgroundBrydon, E. M., Bronstein, R., Buskin, A., Lako, M., Pierce, E. A., & Fernandez-Godino, R. (2019) · doi:10.1101/729160 · Cited by 56
Fundus autofluorescence in uveitis: from pathogenesis to imaging interpretation
Saturno, M. C., Neri, P., & Pichi, F. (2023) · International Ophthalmology · doi:10.1007/s10792-023-02803-1 · Cited by 3
“Typically, the RPE cells engulf and digest the outer photoreceptor segments daily [6].”
Proof of Principle: Preclinical Data on Retinal Cell Transplantation
Hudspith, K., Xue, G., & Singh, M. S. (2019) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-030-05222-5_2 · Cited by 3
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Choi, J. A., Seo, B.-R., Koh, J., & Yoon, Y. H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e39100 · Cited by 2
Preclinical Foundations: Relevant Anatomy and Physiology
Browning, D. J. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0597-3_1 · Cited by 2
Loss of CIB2 causes non-canonical autophagy deficits and visual impairmentPreprint
Sethna, S., Scott, P. A., Giese, A. P. J., Duncan, T. E., Redmond, T. M., Riazuddin, S., & Ahmed, Z. M. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.18.302174 · Cited by 2
Microglial Bmal1 Contributes to Diurnal Physiology and Retinal Homeostasis
Pfeifer, C. W., Santeford, A. C., & Apte, R. S. (2025) · Glia · doi:10.1002/glia.70061 · Cited by 1
“Given that features of RPE and photoreceptor physiology, such as outer segment shedding and the visual cycle, are intrinsically circadian, we may be observing morphological and ultrastructural defects that result from their dysregulation (Bosch et al. 1993; Finnemann et al. 1997).”
√ñzg√o√ß, M., Eldem, T., Durlu, Y. K., et al. (2002) · CRC Press eBooks · doi:10.1201/9780203219935.ch16 · Cited by 1
Sánchez, A. G., Colucci, P., Moran, A. L., López, A. M., Colligris, B., Álvarez, Y., & Kennedy, B. N. (2023) · Open Research Europe · doi:10.12688/openreseurope.15491.1 · Cited by 1
Babu, K. A., Sen, P., Biswas, J., & Angayarkanni, N. (2022) · Research Square · doi:10.21203/rs.3.rs-1647955/v1 · Cited by 1
An Unexpected Role for GPR143 in Retinal HomeostasisPreprint
Tung, D., Congrove, N. R., Figueroa, A. G., Bliss, R. M., Zvavamwe, T., & McKay, B. S. (2023) · Preprints.org · doi:10.20944/preprints202301.0094.v1 · Cited by 1
Investigation of the role of putative chaperones in retinal degeneration
Novoselova, T. V. (2009) · UCL Discovery (University College London)
Phagocytosis of Retinal Rod and Cone Photoreceptors
Farnoodian, M., Kinter, J. B., Aghdam, S. Y., Zaitoun, I. S., Christine, M. S., Khoh‐Reiter, S., Sokolowski, S. A., Jessen, B. A., Evans, M. G., Dalvie, D., et al. (2015)
Dietary Antioxidants, αvβ5 Integrin, and Ocular Protection
Sethna, S., & Finnemann, S. C. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-401717-7.00058-7
A systemically-delivered stem cell therapy for dry age related macular degeneration
Pay, S. L. (2017) · IUScholarWorks (Indiana University) · doi:10.7912/c2006q
“[55] RPE cells contain several organelles including lysosomes, [56] phagosomes, [57] microperoxisomes, [58] and melanosomes.”
BackgroundCell-Based Therapies to Restrict the Progress of Photoreceptor Degeneration
Lund, R. D., & Wang, S. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-186-4_17
CDK5 activity in retinal pigment epithelium contributes to gap junction dynamics during phagocytosisPreprint
Fadjukov, J., Wienbar, S. R., Milićević, N., Hakanen, S., Vihinen‐Ranta, M., Ihalainen, T. O., Schwartz, G. W., & Nymark, S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.09.527850
“The reported timescale of the phagocytosis in vivo (Bosch et al., 1993; LaVail, 1976) coincides with the half-live for gap junctions (Laird et al., 1991; Rhett et al., 2011).”
BackgroundMüller, C., & Finnemann, S. C. (2024) · Springer eBooks · doi:10.1007/978-3-031-35055-9_3
Impact of Oxidized Lipids in the pathogenic mechanism of Age-Related Macular Degeneration
Angayarkanni, N., Babu, K. A., Raman, R., & Biswas, J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19116-9.00046-4
Karg, M. M., Moorefield, M., Hoffmann, E., Philipose, H., Krasniqi, D., Hoppe, C., Shu, D. Y., Shirahama, S., Ksander, B. R., & Saint‐Geniez, M. (2023) · Figshare · doi:10.6084/m9.figshare.24311671
Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise
Constable, P. A., Loh, L., Habjan, M. Š., et al. (2026) · Documenta Ophthalmologica · doi:10.1007/s10633-026-10103-z
Metadata
- Authors
- Bosch, E., Horwitz, J., & Bok, D.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Journal of Histochemistry & Cytochemistry
- Publisher
- SAGE Publications
- Published
- 1993-02
- Volume
- 41
- Issue
- 2
- Pages
- 253-263
- ISSN
- 0022-1554 (ISSN-L)
- 1551-5044
- OpenAlex
- W1987319020
- Cited by
- 147
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 11 · 2014: 9 · 2013: 5 · 2012: 7
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Histochemistry & Cytochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY-00444, EY-00331, EY3897)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- phagocytosis, rod outer segments, retinal pigment epithelium, lysosome fusion, phagolysosomes, cathepsin D, circadian rhythm, light entrainment, photoreceptors, lysosomal enzymes
- MeSH terms
- Animals, Circadian Rhythm, Freeze Drying, Freezing, Light, Lysosomes, Models, Biological, Phagocytosis, Phagosomes, Pigment Epithelium of Eye, Rod Cell Outer Segment, Microscopy, Immunoelectron, Rats
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