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Article ; Online: Lipoxins A

Livne-Bar, Izhar / Maurya, Shubham / Gronert, Karsten / Sivak, Jeremy M

2024 Volume 21, Issue 1, Page(s) 18

Abstract: Lipoxins are small lipids that are potent endogenous mediators of systemic inflammation resolution in a variety of diseases. We previously reported that Lipoxins ... ...

Abstract	Lipoxins are small lipids that are potent endogenous mediators of systemic inflammation resolution in a variety of diseases. We previously reported that Lipoxins A
MeSH term(s)	Inflammation/chemically induced ; Lipopolysaccharides/toxicity ; Lipoxins/pharmacology ; Lipoxins/metabolism ; Neuroglia/metabolism ; Neuroinflammatory Diseases ; Receptors, CXCR3 ; Animals
Chemical Substances	Lipopolysaccharides ; Lipoxins ; Receptors, CXCR3
Language	English
Publishing date	2024-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-024-03010-0
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Article: Protective Effects of Lipoxin A

Liu, Hsin-Hua / Cullen, Paul F / Sivak, Jeremy M / Gronert, Karsten / Flanagan, John G

bioRxiv : the preprint server for biology

2024

Abstract: Glaucoma is a common neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the retinal nerve fiber layer (RNFL), resulting in a gradual decline of vision. A recent study by our groups indicated that the ... ...

Abstract	Glaucoma is a common neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the retinal nerve fiber layer (RNFL), resulting in a gradual decline of vision. A recent study by our groups indicated that the levels of lipoxins A
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.17.575414
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Article ; Online: An inducible rodent glaucoma model that exhibits gradual sustained increase in intraocular pressure with distinct inner retina and optic nerve inflammation.

Mathew, David J / Livne-Bar, Izhar / Sivak, Jeremy M

Scientific reports

2021 Volume 11, Issue 1, Page(s) 22880

Abstract: Glaucoma is a chronic and progressive neurodegenerative disease of the optic nerve resulting in loss of retinal ganglion cells (RGCs) and vision. The most prominent glaucoma risk factor is increased intraocular pressure (IOP), and most models focus on ... ...

Abstract	Glaucoma is a chronic and progressive neurodegenerative disease of the optic nerve resulting in loss of retinal ganglion cells (RGCs) and vision. The most prominent glaucoma risk factor is increased intraocular pressure (IOP), and most models focus on reproducing this aspect to study disease mechanisms and targets. Yet, current models result in IOP profiles that often do not resemble clinical glaucoma. Here we introduce a new model that results in a gradual and sustained IOP increase over time. This approach modifies a circumlimbal suture method, taking care to make the sutures 'snug' instead of tight, without inducing an initial IOP spike. This approach did not immediately affect IOPs, but generated gradual ocular hypertension (gOHT) as the sutures tighten over time, in comparison to loosely sutured control eyes (CON), resulting in an average 12.6 mmHg increase in IOP at 17 weeks (p < 0.001). Corresponding characterization revealed relevant retinal and optic nerve pathology, such as thinning of the retinal nerve fiber layer, decreased optokinetic response, RGC loss, and optic nerve head remodeling. Yet, angles remained open, with no evidence of inflammation. Corresponding biochemical profiling indicated significant increases in TGF-β2 and 3, and IL-1 family cytokines in gOHT optic nerve tissues compared to CON, with accompanying microglial reactivity, consistent with active tissue injury and repair mechanisms. Remarkably, this signature was absent from optic nerves following acute ocular hypertension (aOHT) associated with intentionally tightened sutures, although the resulting RGC loss was similar in both methods. These results suggest that the pattern of IOP change has an important impact on underlying pathophysiology.
MeSH term(s)	Animals ; Disease Models, Animal ; Disease Progression ; Glaucoma/etiology ; Glaucoma/metabolism ; Glaucoma/pathology ; Glaucoma/physiopathology ; Inflammation Mediators/metabolism ; Interleukin-1/metabolism ; Intraocular Pressure ; Neuroinflammatory Diseases/etiology ; Neuroinflammatory Diseases/metabolism ; Neuroinflammatory Diseases/pathology ; Neuroinflammatory Diseases/physiopathology ; Optic Nerve/metabolism ; Optic Nerve/pathology ; Optic Nerve/physiopathology ; Rats, Long-Evans ; Retina/metabolism ; Retina/pathology ; Retina/physiopathology ; Suture Techniques ; Time Factors ; Transforming Growth Factor beta2/metabolism ; Transforming Growth Factor beta3/metabolism ; Rats
Chemical Substances	Inflammation Mediators ; Interleukin-1 ; Tgfb2 protein, rat ; Tgfb3 protein, rat ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3
Language	English
Publishing date	2021-11-24
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-02057-w
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Article ; Online: Conserved characteristics of ocular refractive development - Did the eye evolve once?

Sivak, Jacob G / Sivak, Jeremy M

Experimental eye research

2018 Volume 183, Page(s) 84–87

Abstract: It has been speculated that the unitary eyes of vertebrates and molluscs, and the compound eyes of insects and crustaceans, evolved separately. On the other hand, the common use of rhodopsin as a photoreceptor molecule, and the conservation of Pax6 as a ... ...

Abstract	It has been speculated that the unitary eyes of vertebrates and molluscs, and the compound eyes of insects and crustaceans, evolved separately. On the other hand, the common use of rhodopsin as a photoreceptor molecule, and the conservation of Pax6 as a master control gene for eye development, suggest instead that the eye evolved once. Yet, recently the molecular genetics that had seemed to suggest a definitive answer to this evolutionary point has once again become cloudy. Here we propose an alternative approach to addressing the question of eye evolution through comparative analyses of physiological optics. Serendipitous discoveries involving form deprivation and defocusing with young monkeys and chicks demonstrated the conserved importance of visual experience on eye development. Similar results have been demonstrated in teleosts, although differences exist in eye anatomy, physiology and optics. In particular, since fish grow throughout life, these effects can also be demonstrated in adults. In comparison, the cephalopod eye is an often-cited example of convergent evolution with the vertebrate eye, although considerable developmental differences exist. Nevertheless, squid eyes from animals raised under alternative lighting exhibit anatomical and refractive changes that agree with those found in vertebrates. Together, these observations provide functional and structural support for the view that the eye evolved once. Because of their very compressed lifespans (only one to two years) cephalopods may be ideal animal models for the study of ocular refractive development.
MeSH term(s)	Animals ; Eye/growth & development ; Eye Proteins/physiology ; Humans ; Refraction, Ocular/physiology
Chemical Substances	Eye Proteins
Language	English
Publishing date	2018-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2018.05.007
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Article ; Online: The aging eye: common degenerative mechanisms between the Alzheimer's brain and retinal disease.

Sivak, Jeremy M

Investigative ophthalmology & visual science

2013 Volume 54, Issue 1, Page(s) 871–880

Abstract: Alzheimer's disease (AD) is a common, incurable, and progressive dementia, characterized by loss of learning and memory and the neuropathologic accumulation of amyloid plaques and neurofibrillary tangles in the brain. A number of similarities between AD ... ...

Abstract	Alzheimer's disease (AD) is a common, incurable, and progressive dementia, characterized by loss of learning and memory and the neuropathologic accumulation of amyloid plaques and neurofibrillary tangles in the brain. A number of similarities between AD pathology and several distinct retinal degenerations have been described, particularly with respect to either glaucoma or age-related macular degeneration (AMD), each a leading cause of vision loss and blindness worldwide. Although comparisons between these diseases may provide important new insights into their pathogenic mechanisms, glaucoma and AMD result in markedly different degenerations. Therefore, analyses of the differences and the similarities between these conditions may prove equally productive. Common mechanisms that appear to underlie all three diseases are explored here, as well as potential use of the retina as a biomarker for AD diagnosis and progression. Based on this comparison, past and current efforts to transfer therapeutic strategies between diseases are discussed.
MeSH term(s)	Aging/pathology ; Alzheimer Disease/pathology ; Animals ; Glaucoma/pathology ; Humans ; Nerve Degeneration/pathology ; Retinal Diseases/pathology
Language	English
Publishing date	2013-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.12-10827
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Article ; Online: Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis.

Vicic, Nevena / Guo, Xiaoxin / Chan, Darren / Flanagan, John G / Sigal, Ian A / Sivak, Jeremy M

Journal of cellular physiology

2022 Volume 237, Issue 9, Page(s) 3687–3702

Abstract: Glaucoma is a common neurodegenerative blinding disease that is closely associated with chronic biomechanical strain at the optic nerve head (ONH). Yet, the cellular injury and mechanosensing mechanisms underlying the resulting damage have remained ... ...

Abstract	Glaucoma is a common neurodegenerative blinding disease that is closely associated with chronic biomechanical strain at the optic nerve head (ONH). Yet, the cellular injury and mechanosensing mechanisms underlying the resulting damage have remained critically unclear. We previously identified Annexin A4 (ANXA4) from a proteomic analyses of human ONH astrocytes undergoing pathological biomechanical strain that mimics glaucomatous conditions. Annexins are a family of calcium-dependent phospholipid binding proteins with key functions in plasma membrane repair (PMR); an active mechanism to limit and mend cellular injury that involves membrane and cytoskeletal reorganizations. However, a role for direct membrane damage and PMR has not been well studied in the context of biomechanical strain, such as that associated with glaucoma. Here we report that this moderate strain surprisingly damages cell membranes to increase permeability in a calcium-dependent manner, and induces rapid aggregation of ANXA4 at injury sites. ANXA4 loss-of-function increases permeability, while exogenous ANXA4 reduces it. Furthermore, ANXA4 aggregation is associated with F-actin dynamics in vitro, and remarkably this interaction and aggregation signature is also observed in the glaucomatous ONH in patient samples. Together these studies link moderate biomechanical strain with direct membrane damage and actin dynamics, and identify an active PMR role for ANXA4 in new model of cell injury associated with glaucoma pathogenesis.
MeSH term(s)	Annexin A4/metabolism ; Calcium/metabolism ; Cell Membrane/metabolism ; Glaucoma/metabolism ; Humans ; Proteomics
Chemical Substances	Annexin A4 ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.30834
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Article ; Online: Deneddylation of ribosomal proteins promotes synergy between MLN4924 and chemotherapy to elicit complete therapeutic responses.

Aubry, Arthur / Pearson, Joel D / Charish, Jason / Yu, Tao / Sivak, Jeremy M / Xirodimas, Dimitris P / Avet-Loiseau, Hervé / Corre, Jill / Monnier, Philippe P / Bremner, Rod

Cell reports

2024 Volume 43, Issue 2, Page(s) 113711

Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113711
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Article ; Online: Fair-Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration.

Kim, Changmo / Livne-Bar, Izhar / Gronert, Karsten / Sivak, Jeremy M

Molecular nutrition & food research

2020 Volume 64, Issue 4, Page(s) e1801076

Abstract: Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)-metabolites, which direct potent ... ...

Abstract	Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)-metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega-6 PUFA. In addition to well-established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.
MeSH term(s)	Animals ; Humans ; Inflammation/metabolism ; Lipoxins/metabolism ; Lipoxins/physiology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurons/metabolism ; Neurons/pathology ; Protein-Lysine 6-Oxidase/metabolism
Chemical Substances	Lipoxins ; Protein-Lysine 6-Oxidase (EC 1.4.3.13)
Language	English
Publishing date	2020-01-07
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201801076
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Article ; Online: All roads lead to glaucoma: Induced retinal injury cascades contribute to a common neurodegenerative outcome.

Alqawlaq, Samih / Flanagan, John G / Sivak, Jeremy M

Experimental eye research

2018 Volume 183, Page(s) 88–97

Abstract: Glaucoma describes a distinct optic neuropathy with complex etiology and a variety of associated risk factors, but with similar pathological endpoints. Risk factors such as age, increased intraocular pressure (IOP), low mean arterial pressure, and ... ...

Abstract	Glaucoma describes a distinct optic neuropathy with complex etiology and a variety of associated risk factors, but with similar pathological endpoints. Risk factors such as age, increased intraocular pressure (IOP), low mean arterial pressure, and autoimmune disease, can all be associated with death of retinal ganglion cells (RGCs) and optic nerve head remodeling. Today, IOP management remains the standard of care, even though IOP elevation is not pathognomonic of glaucoma, and patients can continue to lose vision despite effective IOP control. A contemporary view of glaucoma as a complex, neurodegenerative disease has developed, along with the recognition of a need for new disease modifying retinal treatment strategies and improved outcomes. However, the distinction between risk factors triggering the disease process and retinal injury responses is not always clear. In this review, we attempt to distinguish between the various triggers, and their association with subsequent key RGC injury mechanisms. We propose that distinct glaucomatous risk factors result in similar retinal and optic nerve injury cascades, including oxidative and metabolic stress, glial reactivity, and altered inflammatory responses, which induce common molecular signals to induce RGC apoptosis. This organization forms a coherent disease framework and presents conserved targets for therapeutic intervention that are not limited to specific risk factors.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Astrocytes/pathology ; Disease Progression ; Glaucoma/complications ; Glaucoma/diagnosis ; Humans ; Intraocular Pressure/physiology ; Neurodegenerative Diseases ; Optic Nerve/pathology ; Optic Nerve Diseases/diagnosis ; Optic Nerve Diseases/etiology ; Optic Nerve Diseases/metabolism ; Oxidative Stress ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/pathology ; Risk Factors
Language	English
Publishing date	2018-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2018.11.005
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Zs.A 163: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Kim, Changmo / Livne‐Bar, Izhar / Gronert, Karsten / Sivak, Jeremy M

Molecular nutrition & food research. 2020 Feb., v. 64, no. 4

2020

Abstract	Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.
Keywords	Alzheimer disease ; animal models ; arachidonic acid ; autocrine signaling ; central nervous system ; etiology ; homeostasis ; inflammation ; neurodegenerative diseases ; neurons ; omega-6 fatty acids
Language	English
Dates of publication	2020-02
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201801076
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