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Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria.
Exp Eye Res. 2018 12; 177:112-116.EE

Abstract

PURPOSE

A critical biological function of retina pigment epithelium (RPE) cells is phagocytosis of photoreceptor outer segment (POS) disc membranes. Mitochondrial damage and dysfunction are associated with RPE cells of age-related macular degeneration (AMD) retinas. In this study, we use a transmitochondrial cybrid model to compare the phagocytic properties of RPE cells that contain AMD mitochondria versus age-matched normal mitochondria and their response to treatment with anti-vascular endothelial growth factor (VEGF) drugs: bevacizumab, ranibizumab, and aflibercept.

METHODS

Cybrids, which are cell lines with identical nuclei but mitochondria (mt) from different subjects, are created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 5) cybrids were treated with 1 μm fluorescent latex beads (1.52 × 107 beads/mL) and either 2.09 μM of bevacizumab, 2.59 μM of ranibizumab, or 5.16 μM of aflibercept. These doses of anti-VEGF drugs are equivalent to intravitreal injections given to AMD patients with choroidal neovascularization. Flow cytometry was performed using the ImageStreamX Mark II to assess phagocytic bead-uptake. The average fold values for bead-uptake and SEM were calculated using GraphPad Prism software.

RESULTS

Normal cybrids showed decreased bead-uptake with a fold value of 0.65 ± 0.103 (p = 0.01) after treatment with bevacizumab, 0.80 ± 0.034 (p = 0.0003) with ranibizumab, and 0.81 ± 0.053 (p = 0.007) with aflibercept compared to the untreated normal cybrids (baseline fold of 1). The bevacizumab-treated, ranibizumab-treated, and aflibercept-treated AMD cybrids had decreased bead-uptake with a fold value of 0.71 ± 0.061 (p = 0.001), 0.70 ± 0.101 (p = 0.02), and 0.74 ± 0.125 (p = 0.07), respectively, compared to the untreated AMD cybrids (baseline fold of 1).

CONCLUSIONS

Our initial findings showed that when treated with bevacizumab and ranibizumab, both AMD cybrids and age-matched normal cybrids had a significant decrease in bead-uptake. A similar decrease in bead-uptake was found in normal cybrids treated with aflibercept and while the AMD values trended lower, they were not significant. This data suggests that anti-VEGF drugs can cause loss of phagocytic function.

Authors+Show Affiliations

Gavin Herbert Eye Institute, University of California, Irvine, CA, 92697, USA.Gavin Herbert Eye Institute, University of California, Irvine, CA, 92697, USA.Gavin Herbert Eye Institute, University of California, Irvine, CA, 92697, USA.Gavin Herbert Eye Institute, University of California, Irvine, CA, 92697, USA.Gavin Herbert Eye Institute, University of California, Irvine, CA, 92697, USA; Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA. Electronic address: mkenney@uci.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30071215

Citation

Vo, Thomas A., et al. "Effects of Bevacizumab, Ranibizumab, and Aflibercept On Phagocytic Properties in Human RPE Cybrids With AMD Versus Normal Mitochondria." Experimental Eye Research, vol. 177, 2018, pp. 112-116.
Vo TA, Abedi S, Schneider K, et al. Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria. Exp Eye Res. 2018;177:112-116.
Vo, T. A., Abedi, S., Schneider, K., Chwa, M., & Kenney, M. C. (2018). Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria. Experimental Eye Research, 177, 112-116. https://doi.org/10.1016/j.exer.2018.07.025
Vo TA, et al. Effects of Bevacizumab, Ranibizumab, and Aflibercept On Phagocytic Properties in Human RPE Cybrids With AMD Versus Normal Mitochondria. Exp Eye Res. 2018;177:112-116. PubMed PMID: 30071215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria. AU - Vo,Thomas A, AU - Abedi,Sina, AU - Schneider,Kevin, AU - Chwa,Marilyn, AU - Kenney,M Cristina, Y1 - 2018/07/30/ PY - 2018/03/12/received PY - 2018/06/13/revised PY - 2018/07/24/accepted PY - 2018/8/3/pubmed PY - 2019/3/7/medline PY - 2018/8/3/entrez KW - Aflibercept KW - Age-related macular degeneration KW - Anti-VEGF KW - Bevacizumab KW - Cybrids KW - Latex beads KW - Mitochondria KW - Phagocytosis KW - Ranibizumab KW - Retinal pigment epithelium SP - 112 EP - 116 JF - Experimental eye research JO - Exp Eye Res VL - 177 N2 - PURPOSE: A critical biological function of retina pigment epithelium (RPE) cells is phagocytosis of photoreceptor outer segment (POS) disc membranes. Mitochondrial damage and dysfunction are associated with RPE cells of age-related macular degeneration (AMD) retinas. In this study, we use a transmitochondrial cybrid model to compare the phagocytic properties of RPE cells that contain AMD mitochondria versus age-matched normal mitochondria and their response to treatment with anti-vascular endothelial growth factor (VEGF) drugs: bevacizumab, ranibizumab, and aflibercept. METHODS: Cybrids, which are cell lines with identical nuclei but mitochondria (mt) from different subjects, are created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 5) cybrids were treated with 1 μm fluorescent latex beads (1.52 × 107 beads/mL) and either 2.09 μM of bevacizumab, 2.59 μM of ranibizumab, or 5.16 μM of aflibercept. These doses of anti-VEGF drugs are equivalent to intravitreal injections given to AMD patients with choroidal neovascularization. Flow cytometry was performed using the ImageStreamX Mark II to assess phagocytic bead-uptake. The average fold values for bead-uptake and SEM were calculated using GraphPad Prism software. RESULTS: Normal cybrids showed decreased bead-uptake with a fold value of 0.65 ± 0.103 (p = 0.01) after treatment with bevacizumab, 0.80 ± 0.034 (p = 0.0003) with ranibizumab, and 0.81 ± 0.053 (p = 0.007) with aflibercept compared to the untreated normal cybrids (baseline fold of 1). The bevacizumab-treated, ranibizumab-treated, and aflibercept-treated AMD cybrids had decreased bead-uptake with a fold value of 0.71 ± 0.061 (p = 0.001), 0.70 ± 0.101 (p = 0.02), and 0.74 ± 0.125 (p = 0.07), respectively, compared to the untreated AMD cybrids (baseline fold of 1). CONCLUSIONS: Our initial findings showed that when treated with bevacizumab and ranibizumab, both AMD cybrids and age-matched normal cybrids had a significant decrease in bead-uptake. A similar decrease in bead-uptake was found in normal cybrids treated with aflibercept and while the AMD values trended lower, they were not significant. This data suggests that anti-VEGF drugs can cause loss of phagocytic function. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/30071215/Effects_of_bevacizumab_ranibizumab_and_aflibercept_on_phagocytic_properties_in_human_RPE_cybrids_with_AMD_versus_normal_mitochondria_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(18)30168-4 DB - PRIME DP - Unbound Medicine ER -