Assessment of Retinal Function and Morphology in Aging Ccl2 Knockout Mice

Vessey, Kirstan A.; Waugh, Michelle; Jobling, Andrew I; Phipps, John; Ho, Tracy; Trogrlic, Lidia; Greferath, Ursula; Fletcher, Erica L.

doi:10.1167/iovs.14-15334

Cited by 21 publications

(31 citation statements)

References 63 publications

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“…32 The 7-day time point was chosen, as previous work has identified that the RPE areas selectively ablated by the nanosecond laser are retiled by this time, 29 while the 90-day time point was chosen to assess for a delayed neovascular response. The cornea of mice was anesthetized with topical Alcaine (0.5%) and the pupils dilated with atropine (1%) and phenylephrine (10%).…”

Section: Fundus Photography and Fluorescein Angiographymentioning

confidence: 99%

“…The posterior eyecups (n ‡ 5 per experimental group) were fixed in 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4 (PB) for 30 minutes and cryoprotected in graded sucrose (10%, 20%, 30%) in PB overnight. 33 For retinal wholemounts, the entire eyecup (retina/choroid/sclera) was processed for immunohistochemistry as described previously 32,34 and specifically below. For retinal sections, the eyecup was embedded in optimal cutting temperature (OCT) compound (Tissue-Tek; Sakura, Torrance, CA, USA), frozen at À208C, and sectioned transversely at 14 lm on a Microm HM550 cryostat (Thermo Scientific, Walldorf, Germany).…”

Section: Immunohistochemistry and Confocal Microscopymentioning

confidence: 99%

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Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina

Vessey

Jobling

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD); however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. METHODS.Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15-0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR.RESULTS. Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium-derived factor, an antiangiogenic factor, was upregulated.CONCLUSIONS. In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.

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Section: Fundus Photography and Fluorescein Angiographymentioning

confidence: 99%

Section: Immunohistochemistry and Confocal Microscopymentioning

confidence: 99%

Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina

Vessey

Jobling

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Ambati et al (Ambati et al, 2003) firstly mentioned that mice deficient in MCP-1 develop cardinal features of AMD, including accumulation of lipofuscin and drusen, photoreceptor atrophy and CNV invation. Vessey et al (Vessey et al, 2015) also showed that MCP-1 is important for preserving RPE and glial (C) Activation of ERK1/2, p38, JNK1/2 and NF-kB induced by 7378 K light at 4 h was significantly suppressed by vitamin C and NAC treatment. Results of are presented as means ± SD (n ¼ 3, *P < 0.05; **P < 0.01; ***P < 0.001 compared with group treated with 7378 K light alone).…”

Section: Discussionmentioning

confidence: 96%

“…As the most important pro-inflammatory chemokines in CXC and CC families, IL-8 and MCP-1 are potent chemoattractants of neutrophils and monocytes, respectively (Baggiolini and Clark-Lewis, 1992;Douglas et al, 1997). A large amount of studies have demonstrated that disrupted expression of these pathological cytokines are correlated with the development of AMD (Ambati et al, 2003;Cascella et al, 2014;Jonas et al, 2012;Pons and Marin-Castano, 2011;Roh et al, 2009;Vessey et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells

Shen

Xie

et al. 2016

Experimental Eye Research

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“…One of the more prominent features that occurs in retinae with age is the accumulation of cells of the innate immune system within the subretinal space . As shown in Figure , immune cells accumulate around some of the lesions associated with AMD, especially reticular pseudodrusen, and have also been reported in association with atrophic areas in retinae with geographic atrophy and or choroidal neovascularisation …”

Section: Changes In Mononuclear Phagocytes In Age Related Macular Degmentioning

confidence: 99%

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Fletcher

2020

Ophthalmic Physiologic Optic

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Purpose Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in industrialised nations. Based on genetics, as well as proteome analysis of drusen, the role the innate immune system in the development and/or progression of the disease is well established. Mononuclear phagocytes, such as microglia and monocytes, play critical roles in innate immunity. Here, the role of retinal microglia in mediating normal retinal function, and how these cells change with age is discussed, so as to understand their role in the development and progression of AMD. Recent findings It is now known that microglia dynamically survey the neural environment, responding rapidly to even the most subtle neural injury. The dynamic and phagocytic roles of microglia can change with age contributing to alteration in the response of these cells to damage with age. Accumulation of innate immune cells in the subretinal space is a hallmark feature of the development of AMD, reflecting either an increase in migration of monocytes into the retina, or a failure of immune cell elimination from the retina. Furthermore, changes in phagocytic ability of immune cells could contribute to the accumulation of drusen deposits in the posterior eye. Summary An overview of how retinal microglia maintain retinal homeostasis under normal conditions is provided, and then how they contribute to each stage of AMD. In addition, circulating monocytes are altered in those with AMD, contributing to the overall inflammatory state. Understanding the role of cells of the innate immune system in AMD may uncover novel therapeutic targets with which to reduce either the development or progression of disease.

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Assessment of Retinal Function and Morphology in Aging Ccl2 Knockout Mice

Abstract: These data show that Ccl2 is important for preserving RPE and glial morphology with age, yet retinal function and gross morphology are maintained. Altered signaling in this chemokine pathway may, however, increase RPE and retinal vulnerability to disease.

Cited by 21 publications

References 63 publications

Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina

Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina

Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

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