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  1. Article ; Online: Shotgun lipidomics of human subretinal fluids under rod-dominant retina reveals cone-dominated lipids.

    Chen, Jianzhong / Curcio, Christine A / Crosson, Jason N

    Experimental eye research

    2024  Volume 240, Page(s) 109807

    Abstract: Subretinal fluid (SRF) accumulates between photoreceptor outer segments and retinal pigment epithelium during rhegmatogenous retinal detachment. Biomolecular components such as lipids originate from cells surrounding the SRF. Knowledge of the composition ...

    Abstract Subretinal fluid (SRF) accumulates between photoreceptor outer segments and retinal pigment epithelium during rhegmatogenous retinal detachment. Biomolecular components such as lipids originate from cells surrounding the SRF. Knowledge of the composition of these molecules in SRF potentially provides mechanistic insight into the physiologic transfer of lipids between retinal tissue compartments. Using mass spectrometry and tandem mass spectrometry analysis on an electrospray ionization quadrupole-time-of-flight mass spectrometer, we identified a total of 115 lipid molecular species of 11 subclasses and 9 classes in two samples from two patients with rhegmatogenous retinal detachment. These included 47 glycerophosphocholines, 6 glycerophosphoethanolamines, 1 glycerophosphoinositol, 18 sphingomyelins, 9 cholesteryl esters, free cholesterol, 3 ceramides, 22 triacylglycerols and 8 free fatty acids. Glycerophosphocholines were of the highest intensity. By minimizing the formation of different adduct forms or clustering ions of different adducts, we determined the relative intensity of lipid molecular species within the same subclasses. The profiles were compared with those of retinal cells available in the published literature. The glycerophosphocholine profile of SRF was similar to that of cone outer segments, suggesting that outer segment degradation products are constitutively released into the interphotoreceptor matrix, appearing in SRF during detachment. This hypothesis was supported by the retinal distributions of corresponding lipid synthases' mRNA expression obtained from an online resource based on publicly available single-cell sequencing data. In contrast, based on lipid profiles and relevant gene expression in this study, the sources of free cholesterol and cholesteryl esters in SRF appeared more ambiguous, possibly reflecting that outer retina takes up plasma lipoproteins. Further studies to identify and quantify lipids in SRF will help better understand etiology of diseases relevant to outer retina.
    MeSH term(s) Humans ; Retinal Detachment/metabolism ; Subretinal Fluid/metabolism ; Cholesterol Esters/metabolism ; Lipidomics ; Retina/metabolism
    Chemical Substances Cholesterol Esters
    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 80122-7
    ISSN 1096-0007 ; 0014-4835
    ISSN (online) 1096-0007
    ISSN 0014-4835
    DOI 10.1016/j.exer.2024.109807
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Optical Coherence Tomography Angiography and Corresponding Histology-Reply.

    Berlin, Andreas / Freund, K Bailey / Curcio, Christine A

    JAMA ophthalmology

    2023  Volume 141, Issue 4, Page(s) 404–405

    MeSH term(s) Humans ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods
    Language English
    Publishing date 2023-02-16
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2701705-9
    ISSN 2168-6173 ; 2168-6165
    ISSN (online) 2168-6173
    ISSN 2168-6165
    DOI 10.1001/jamaophthalmol.2022.6352
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  3. Article ; Online: Cholesteryl Ester Transfer Protein Inhibitors and Access to the Retina in Age-Related Macular Degeneration.

    Curcio, Christine A / Johnson, Mark

    JAMA cardiology

    2022  Volume 8, Issue 2, Page(s) 206

    MeSH term(s) Humans ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL/metabolism ; Macular Degeneration/drug therapy ; Retina/metabolism
    Chemical Substances Cholesterol Ester Transfer Proteins ; Cholesterol, HDL
    Language English
    Publishing date 2022-12-28
    Publishing country United States
    Document type Letter ; Comment
    ISSN 2380-6591
    ISSN (online) 2380-6591
    DOI 10.1001/jamacardio.2022.4808
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  4. Article: Rod mediated dark adaptation, a functional test for early and intermediate AMD outcomes.

    Owsley, Cynthia / Swain, Thomas A / Kar, Deepayan / Curcio, Christine A

    Expert review of ophthalmology

    2023  Volume 19, Issue 1, Page(s) 1–5

    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ISSN 1746-9899
    ISSN 1746-9899
    DOI 10.1080/17469899.2023.2287178
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  5. Article ; Online: Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula.

    Curcio, Christine A

    Investigative ophthalmology & visual science

    2019  Volume 59, Issue 4, Page(s) AMD182–AMD194

    Abstract: AMD pathobiology was irreversibly changed by the recent discovery of extracellular cholesterol-containing deposits in the subretinal space, between the photoreceptors and retinal pigment epithelium (RPE), called subretinal drusenoid deposits (SDDs). SDDs ...

    Abstract AMD pathobiology was irreversibly changed by the recent discovery of extracellular cholesterol-containing deposits in the subretinal space, between the photoreceptors and retinal pigment epithelium (RPE), called subretinal drusenoid deposits (SDDs). SDDs strikingly mirror the topography of rod photoreceptors in human macula, raising the question of whether an equivalent process results in a deposition related to foveal cones. Herein we propose that AMD's pathognomonic lesion-soft drusen and basal linear deposit (BLinD, same material, diffusely distributed)-is the leading candidate. Epidemiologic, clinical, and histologic data suggest that these deposits are most abundant in the central macula, under the fovea. Strong evidence presented in a companion article supports the idea that the dominant ultrastructural component is large apolipoprotein B,E-containing lipoproteins, constitutively secreted by RPE. Lipoprotein fatty acids are dominated by linoleate (implicating diet) rather than docosahexaenoate (implicating photoreceptors); we seek within the retina cellular relationships and dietary drivers to explain soft druse topography. The delivery of xanthophyll pigments to highly evolved and numerous Müller cells in the human fovea, through RPE, is one strong candidate, because Müller cells are the main reservoir of these pigments, which replenish from diet. We propose that the evolution of neuroglial relations and xanthophyll delivery that underlie exquisite human foveal vision came with a price, that is, soft drusen and sequela, long after our reproductive years.
    MeSH term(s) Apolipoproteins B/metabolism ; Apolipoproteins E/metabolism ; Humans ; Macula Lutea/metabolism ; Macular Degeneration/metabolism ; Macular Degeneration/physiopathology ; Retinal Drusen/metabolism ; Retinal Drusen/physiopathology ; Retinal Pigment Epithelium/metabolism ; Xanthophylls/metabolism
    Chemical Substances Apolipoproteins B ; Apolipoproteins E ; Xanthophylls
    Language English
    Publishing date 2019-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.18-24883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.

    Curcio, Christine A

    Investigative ophthalmology & visual science

    2019  Volume 59, Issue 4, Page(s) AMD160–AMD181

    Abstract: AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascular-metabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/basal ...

    Abstract AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascular-metabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/basal linear deposit (BLinD) and subretinal drusenoid deposit (SDD), confer risk for end-stages of atrophy and neovascularization. Understanding how deposits form can lead to insights for new preventions and therapy. The topographic correspondence of BLinD and SDD with cones and rods, respectively, suggest newly realized exchange pathways among outer retinal cells and across Bruch's membrane and the subretinal space, in service of highly evolved, eye-specific physiology. This review focuses on soft drusen/BLinD, summarizing evidence that a major ultrastructural component is large apolipoprotein B,E-containing, cholesterol-rich lipoproteins secreted by the retinal pigment epithelium (RPE) that offload unneeded lipids of dietary and outer segment origin to create an atherosclerosis-like progression in the subRPE-basal lamina space. Clinical observations and an RPE cell culture system combine to suggest that soft drusen/BLinD form when secretions of functional RPE back up in the subRPE-basal lamina space by impaired egress across aged Bruch's membrane-choriocapillary endothelium. The soft drusen lifecycle includes growth, anterior migration of RPE atop drusen, then collapse, and atrophy. Proof-of-concept studies in humans and animal models suggest that targeting the "Oil Spill in Bruch's membrane" offers promise of treating a process in early AMD that underlies progression to both end-stages. A companion article addresses the antecedents of soft drusen within the biology of the macula.
    MeSH term(s) Apolipoproteins B/metabolism ; Apolipoproteins E/metabolism ; Humans ; Macular Degeneration/physiopathology ; Retinal Drusen/metabolism ; Retinal Drusen/physiopathology ; Retinal Pigment Epithelium/metabolism
    Chemical Substances Apolipoproteins B ; Apolipoproteins E
    Language English
    Publishing date 2019-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.18-24882
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Viewing Retinal Vasculature in Alzheimer Disease.

    Curcio, Christine A

    JAMA ophthalmology

    2018  Volume 136, Issue 11, Page(s) 1249–1250

    MeSH term(s) Alzheimer Disease ; Angiography ; Humans ; Retina ; Retinal Vessels ; Tomography, Optical Coherence
    Language English
    Publishing date 2018-12-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2701705-9
    ISSN 2168-6173 ; 2168-6165
    ISSN (online) 2168-6173
    ISSN 2168-6165
    DOI 10.1001/jamaophthalmol.2018.3569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: A New Online Portal Will Match Eye Banks With Researchers Seeking Human Ocular Tissues.

    Curcio, Christine A

    Investigative ophthalmology & visual science

    2018  Volume 59, Issue 12, Page(s) 4796–4797

    MeSH term(s) Corneal Transplantation ; Cross-Sectional Studies ; Eye Banks ; Humans ; Surveys and Questionnaires
    Language English
    Publishing date 2018-10-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.18-25632
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Age-Related Macular Degeneration, a Mathematically Tractable Disease.

    Curcio, Christine A / Kar, Deepayan / Owsley, Cynthia / Sloan, Kenneth R / Ach, Thomas

    Investigative ophthalmology & visual science

    2024  Volume 65, Issue 3, Page(s) 4

    Abstract: A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early ... ...

    Abstract A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
    MeSH term(s) Humans ; Adult ; Aged ; Macular Degeneration ; Retina ; Macula Lutea ; Geographic Atrophy ; Retinal Cone Photoreceptor Cells
    Language English
    Publishing date 2024-03-11
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.65.3.4
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  10. Article ; Online: Isolation, culture, and cryosectioning of primary porcine retinal pigment epithelium on transwell cell culture inserts.

    Hood, Erika M S / Curcio, Christine A / Lipinski, Daniel

    STAR protocols

    2022  Volume 3, Issue 4, Page(s) 101758

    Abstract: Primary culture and long-term maintenance of primary retinal pigment epithelium (RPE) is a useful model system for the study of ocular pathologies such as age-related macular degeneration. Here, we detail the steps for the isolation and long-term culture ...

    Abstract Primary culture and long-term maintenance of primary retinal pigment epithelium (RPE) is a useful model system for the study of ocular pathologies such as age-related macular degeneration. Here, we detail the steps for the isolation and long-term culture of primary porcine RPE. We also describe steps for cryoprotecting, cryosectioning, and interrogating with immunofluorescence and histochemistry RPE cells grown on transwell membranes. These techniques can be used in histological studies to detect sub-RPE deposits. For complete details on the use and execution of this protocol, please refer to Pilgrim et al., (2017).
    MeSH term(s) Swine ; Animals ; Retinal Pigment Epithelium ; Macular Degeneration/metabolism ; Macular Degeneration/pathology ; Cell Culture Techniques ; Models, Biological ; Cryoultramicrotomy
    Language English
    Publishing date 2022-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101758
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