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  1. Article ; Online: Intraluminal Deposits Found in Glaucoma Tube Shunts Via Anterior Segment Ocular Coherence Tomography.

    Alvarado, Jorge A / Srivastava, Vinita / Sun, Yang

    Journal of glaucoma

    2017  Volume 27, Issue 3, Page(s) e68–e71

    Abstract: Purpose: To describe and characterize a novel observation of intraluminal deposits of glaucoma tube shunts (TS) using spectral domain (SD) ocular coherence topography (OCT).: Patients and methods: Fifteen TS in 11 patients diagnosed with primary open- ...

    Abstract Purpose: To describe and characterize a novel observation of intraluminal deposits of glaucoma tube shunts (TS) using spectral domain (SD) ocular coherence topography (OCT).
    Patients and methods: Fifteen TS in 11 patients diagnosed with primary open-angle, neovascular, aphakic, and uveitic glaucomas. Both Ahmed (n=11) and Baerveldt (n=4) TS were examined with 5-line raster anterior segment SD-OCT imaging.
    Results: The exposed tubes of 2 patients had highly reflective intraluminal deposits in the corresponding exposed areas. Seven tubes without exposure had a thin rim of highly reflective material. Six tubes were clear of luminal deposits. The most common diagnosis in the study was uveitic glaucoma which occurred in 5 of the 15 eyes (33%). The next most common diagnosis was primary open-angle glaucoma which occurred in 4 of the 15 eyes (25%). There were 2 nonvalved Baerveldt tubes in each group. The mean duration of TS implantation was 15.0 months in the deposit group and 33.7 months in the group without luminal deposits. The majority of patients in each group were using eye drops at presentation (88.9% deposit, 83.3% clear), and the average intraocular pressure was 20.2 mm Hg in the deposit group and 19.0 mm Hg in the clear group.
    Conclusions: Anterior segment OCT imaging may be used to evaluate TS integrity. Intraluminal deposits in TS may occur as a natural response to implanted drainage device, possibly as an inflammatory response.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Anterior Chamber/diagnostic imaging ; Anterior Chamber/surgery ; Chemical Precipitation ; Drainage/instrumentation ; Equipment Failure Analysis/methods ; Female ; Glaucoma/diagnosis ; Glaucoma/physiopathology ; Glaucoma/surgery ; Glaucoma Drainage Implants/adverse effects ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology ; Prosthesis Failure ; Prosthesis Implantation/adverse effects ; Prosthesis Implantation/methods ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Tonometry, Ocular
    Language English
    Publishing date 2017-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 913494-3
    ISSN 1536-481X ; 1057-0829
    ISSN (online) 1536-481X
    ISSN 1057-0829
    DOI 10.1097/IJG.0000000000000840
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Reduced ocular allergy with fixed-combination 0.2% brimonidine-0.5% timolol.

    Alvarado, Jorge A

    Archives of ophthalmology (Chicago, Ill. : 1960)

    2007  Volume 125, Issue 5, Page(s) 717; author reply 717–8

    MeSH term(s) Antihypertensive Agents/administration & dosage ; Antihypertensive Agents/adverse effects ; Antihypertensive Agents/therapeutic use ; Brimonidine Tartrate ; Clinical Trials as Topic ; Conjunctivitis, Allergic/chemically induced ; Drug Therapy, Combination ; Glaucoma, Open-Angle/drug therapy ; Humans ; Intraocular Pressure ; Ocular Hypertension/drug therapy ; Quinoxalines/administration & dosage ; Quinoxalines/adverse effects ; Quinoxalines/therapeutic use ; Timolol/administration & dosage ; Timolol/adverse effects ; Timolol/therapeutic use
    Chemical Substances Antihypertensive Agents ; Quinoxalines ; Brimonidine Tartrate (4S9CL2DY2H) ; Timolol (817W3C6175)
    Language English
    Publishing date 2007-05
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 211580-3
    ISSN 1538-3601 ; 0003-9950 ; 0093-0326
    ISSN (online) 1538-3601
    ISSN 0003-9950 ; 0093-0326
    DOI 10.1001/archopht.125.5.717-a
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  3. Article: Endocyclophotocoagulation for pediatric glaucoma: a tale of two cities.

    Alvarado, Jorge A

    Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus

    2007  Volume 11, Issue 1, Page(s) 10–11

    MeSH term(s) Child ; Child, Preschool ; Ciliary Body/surgery ; Glaucoma/surgery ; Humans ; Infant ; Intraocular Pressure ; Laser Coagulation ; Prognosis
    Language English
    Publishing date 2007-02
    Publishing country United States
    Document type Case Reports ; Comment ; Editorial
    ZDB-ID 1412476-2
    ISSN 1528-3933 ; 1091-8531
    ISSN (online) 1528-3933
    ISSN 1091-8531
    DOI 10.1016/j.jaapos.2006.11.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring.

    Wang, Biao / He, Wei / Prosseda, Philipp P / Li, Liang / Kowal, Tia J / Alvarado, Jorge A / Wang, Qing / Hu, Yang / Sun, Yang

    EMBO reports

    2021  Volume 22, Issue 7, Page(s) e52173

    Abstract: Lysosomal positioning and mTOR (mammalian target of rapamycin) signaling coordinate cellular responses to nutrient levels. Inadequate nutrient sensing can result in growth delays, a hallmark of Lowe syndrome. OCRL mutations cause Lowe syndrome, but the ... ...

    Abstract Lysosomal positioning and mTOR (mammalian target of rapamycin) signaling coordinate cellular responses to nutrient levels. Inadequate nutrient sensing can result in growth delays, a hallmark of Lowe syndrome. OCRL mutations cause Lowe syndrome, but the role of OCRL in nutrient sensing is unknown. Here, we show that OCRL is localized to the centrosome by its ASH domain and that it recruits microtubule-anchoring factor SSX2IP to the centrosome, which is important in the formation of the microtubule-organizing center. Deficiency of OCRL in human and mouse cells results in loss of microtubule-organizing centers and impaired microtubule-based lysosome movement, which in turn leads to mTORC1 inactivation and abnormal nutrient sensing. Centrosome-targeted PACT-SSX2IP can restore microtubule anchoring and mTOR activity. Importantly, boosting the activity of mTORC1 restores the nutrient sensing ability of Lowe patients' cells. Our findings highlight mTORC1 as a novel therapeutic target for Lowe syndrome.
    MeSH term(s) Animals ; Cell Cycle Proteins ; Humans ; Lysosomes ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mice ; Microtubule-Associated Proteins ; Microtubules ; Oculocerebrorenal Syndrome ; Phosphoric Monoester Hydrolases
    Chemical Substances Cell Cycle Proteins ; Microtubule-Associated Proteins ; SSX2IP protein, human ; Ssx2ip protein, mouse ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; OCRL protein, human (EC 3.1.3.36) ; Ocrl protein, mouse (EC 3.1.3.36)
    Language English
    Publishing date 2021-05-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202052173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Management of plateau iris syndrome with cataract extraction and endoscopic cyclophotocoagulation.

    Hollander, David A / Pennesi, Mark E / Alvarado, Jorge A

    Experimental eye research

    2016  Volume 158, Page(s) 190–194

    Abstract: Plateau iris configuration describes an anatomic abnormality in which large or anteriorly positioned pars plicata push the iris root forward, thereby narrowing the anterior chamber angle. Plateau iris syndrome (PIS) is diagnosed if the angle remains ... ...

    Abstract Plateau iris configuration describes an anatomic abnormality in which large or anteriorly positioned pars plicata push the iris root forward, thereby narrowing the anterior chamber angle. Plateau iris syndrome (PIS) is diagnosed if the angle remains occludable, either spontaneously or pharmacologically, after iridotomy. PIS has traditionally been treated with chronic pilocarpine or laser peripheral iridoplasty. A series of 9 eyes of 6 patients with PIS, diagnosed by dark room provocative testing and ultrasound biomicroscopy (UBM) following iridotomy, underwent cataract extraction and endoscopic cyclophotocoagulation (ECP). The ciliary body was treated for a median of 180° (range of 120-360°). Post-ECP, the angles in areas treated with ECP were open with corresponding flattened ciliary processes on UBM, while the angles remained occludable in quadrants untreated by ECP despite lens extraction. The mean follow-up time post-ECP was 73.7 ± 34 months (range 11-122 months). The mean IOP was reduced from a baseline of 25.2 ± 10.9 mm Hg on 3.4 ± 1.0 IOP lowering medications to a mean IOP of 17.1 ± 5.3 mm Hg (p < 0.05) on 1.9 ± 1.5, (p < 0.01) medications at last visit. There were no cases of chronic inflammation, eye pain, decreased vision, retinal detachment, or hypotony. Lens extraction and ECP offers an alternative treatment option for patients with PIS, which may directly address the underlying anatomic abnormality leading to angle closure in PIS.
    MeSH term(s) Aged ; Aged, 80 and over ; Cataract Extraction ; Ciliary Body/diagnostic imaging ; Ciliary Body/surgery ; Endoscopy ; Female ; Glaucoma, Angle-Closure/surgery ; Humans ; Intraocular Pressure/physiology ; Iris Diseases/diagnostic imaging ; Iris Diseases/surgery ; Laser Coagulation/methods ; Lasers, Gas/therapeutic use ; Male ; Microscopy, Acoustic ; Middle Aged ; Tonometry, Ocular
    Language English
    Publishing date 2016-07-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80122-7
    ISSN 1096-0007 ; 0014-4835
    ISSN (online) 1096-0007
    ISSN 0014-4835
    DOI 10.1016/j.exer.2016.07.018
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  6. Article ; Online: Endoscopic Cyclophotocoagulation and Other Cyclodestructive Methods: Histopathologic Comparison of In Vivo Treatment in Humans and Monkeys.

    Francis, Brian A / Flowers, Brian / Dastiridou, Anna / Yelenskiy, Aleksandr / Chopra, Vikas / Alvarado, Jorge A

    Ophthalmology. Glaucoma

    2019  Volume 2, Issue 6, Page(s) 413–421

    Abstract: Purpose: To compare the histologic effects of endoscopic cyclophotocoagulation (ECP) with other ciliary body ablative procedures. A secondary aim was to correlate these findings with historical clinical success and complication rates.: Design: ... ...

    Abstract Purpose: To compare the histologic effects of endoscopic cyclophotocoagulation (ECP) with other ciliary body ablative procedures. A secondary aim was to correlate these findings with historical clinical success and complication rates.
    Design: Prospective, qualitative comparison of histopathologic tissue analysis.
    Participants: Two eyes of two patients who had undergone ECP for open-angle glaucoma were studied. Two eyes from a healthy monkey were treated with ECP and studied. For comparison, 1 eye each of patients who had undergone contact and noncontact neodymium:yttrium-aluminum-garnet transscleral cyclophotocoagulation (TCP) for open-angle glaucoma were analyzed.
    Methods: The human globes were enucleated and submitted for analysis by gross examination and light and electron microscopy. Monkey eyes were studied by gross examination and light microscopy 1 week, 2 weeks, and 1 month after ECP.
    Main outcome measures: Gross and histopathologic specimens of all eyes were analyzed with respect to location and type of tissue effects and degree of collateral damage.
    Results: The gross analysis of all ECP specimens showed a uniform anterior-to-posterior whitening of each treated ciliary process. This correlated with microscopic evidence of loss of pigmentation from the pigmented ciliary epithelial cells seen with mostly preserved architecture and vasculature of the ciliary processes. By comparison, the TCP specimens showed erratic treatment of the ciliary processes with overlap into the pars plicata of the ciliary body. Microscopic analysis revealed significant disruption of the cells throughout the ciliary processes and loss of vessels within the stroma.
    Conclusions: Treatment with ECP results in less overall tissue destruction and a targeted effect on the pigmented ciliary epithelium of the ciliary processes when compared with TCP.
    MeSH term(s) Animals ; Ciliary Body/pathology ; Ciliary Body/surgery ; Disease Models, Animal ; Endoscopy/methods ; Glaucoma/pathology ; Glaucoma/physiopathology ; Glaucoma/surgery ; Haplorhini ; Humans ; Intraocular Pressure/physiology ; Laser Coagulation/methods
    Language English
    Publishing date 2019-09-04
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ISSN 2589-4196
    ISSN (online) 2589-4196
    DOI 10.1016/j.ogla.2019.08.008
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  7. Article ; Online: Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation.

    Prosseda, Philipp P / Alvarado, Jorge A / Wang, Biao / Kowal, Tia J / Ning, Ke / Stamer, W Daniel / Hu, Yang / Sun, Yang

    Science advances

    2020  Volume 6, Issue 18, Page(s) eaay8699

    Abstract: Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well ... ...

    Abstract Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well understood. Here, we have designed CIBN/CRY2-based optogenetic constructs to study phosphoinositide regulation within distinct subcellular compartments. We show that stimulation of CRY2-OCRL, an inositol 5-phosphatase, increases aqueous humor outflow and lowers IOP in vivo, which is caused by a calcium-dependent actin rearrangement of the trabecular meshwork cells. Phosphoinositide stimulation also rescues defective aqueous outflow and IOP in a Lowe syndrome mouse model but not in IFT88
    Language English
    Publishing date 2020-04-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.aay8699
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  8. Article ; Online: Developmental distribution of primary cilia in the retinofugal visual pathway.

    Alvarado, Jorge A / Dhande, Onkar S / Prosseda, Philipp P / Kowal, Tia J / Ning, Ke / Jabbehdari, Sayena / Hu, Yang / Sun, Yang

    The Journal of comparative neurology

    2020  Volume 529, Issue 7, Page(s) 1442–1455

    Abstract: The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus ( ... ...

    Abstract The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), bridge retinal input and visual output. The primary cilium is a conserved organelle increasingly viewed as a critical sensor for the regulation of developmental and homeostatic pathways in most mammalian cell types. Moreover, cilia have been described as crucial for neurogenesis, neuronal maturation, and survival in the cortex and retina. However, cilia in the visual relay center remain to be fully described. In this study, we characterized the ciliation profile of the SC and dLGN and found that the overall number of ciliated cells declined during development. Interestingly, shorter ciliated cells in both regions were identified as neurons, whose numbers remained stable over time, suggesting that cilia retention is a critical feature for optimal neuronal function in SC and dLGN. Our study suggests that primary cilia are important for neuronal maturation and function in cells of the SC and dLGN.
    MeSH term(s) Animals ; Cilia/ultrastructure ; Geniculate Bodies/ultrastructure ; Macaca mulatta ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Neurogenesis/physiology ; Neurons/ultrastructure ; Superior Colliculi/ultrastructure ; Visual Pathways/physiology ; Visual Pathways/ultrastructure
    Language English
    Publishing date 2020-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.25029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Progress towards understanding the functioning of the trabecular meshwork based on lessons from studies of laser trabeculoplasty.

    Alvarado, Jorge A / Shifera, Amde Selassie

    The British journal of ophthalmology

    2010  Volume 94, Issue 11, Page(s) 1417–1418

    MeSH term(s) Humans ; Laser Therapy/methods ; Trabecular Meshwork/physiology ; Trabeculectomy/methods
    Language English
    Publishing date 2010-11
    Publishing country England
    Document type Comment ; Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80078-8
    ISSN 1468-2079 ; 0007-1161
    ISSN (online) 1468-2079
    ISSN 0007-1161
    DOI 10.1136/bjo.2010.182543
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  10. Article ; Online: Loss of OCRL increases ciliary PI(4,5)P

    Prosseda, Philipp P / Luo, Na / Wang, Biao / Alvarado, Jorge A / Hu, Yang / Sun, Yang

    Journal of cell science

    2017  Volume 130, Issue 20, Page(s) 3447–3454

    Abstract: Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5) ... ...

    Abstract Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P
    MeSH term(s) Animals ; Cell Line ; Cilia/metabolism ; Hedgehog Proteins/physiology ; Humans ; Mice ; Mice, Knockout ; Oculocerebrorenal Syndrome/genetics ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phosphoric Monoester Hydrolases/genetics ; Phosphoric Monoester Hydrolases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Second Messenger Systems ; Smoothened Receptor/metabolism
    Chemical Substances GPR161 protein, human ; Hedgehog Proteins ; Phosphatidylinositol 4,5-Diphosphate ; Receptors, G-Protein-Coupled ; Smo protein, mouse ; Smoothened Receptor ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; OCRL protein, human (EC 3.1.3.36)
    Language English
    Publishing date 2017-09-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.200857
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