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Article ; Online: A Coming of Age for Glaucoma Neuroprotection.

Johnson, Thomas V

Ophthalmology science

2023 Volume 3, Issue 2, Page(s) 100304

Language	English
Publishing date	2023-04-06
Publishing country	Netherlands
Document type	Editorial ; Comment
ISSN	2666-9145
ISSN (online)	2666-9145
DOI	10.1016/j.xops.2023.100304
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Article ; Online: Analyses of transplanted human retinal ganglion cell morphology and localization in murine organotypic retinal explant culture.

Zhang, Kevin Y / Johnson, Thomas V

STAR protocols

2022 Volume 3, Issue 2, Page(s) 101328

Abstract: Retinal ganglion cell (RGC) transplantation has the potential to restore vision in optic neuropathy, but donor neuron survival and retinal integration remain challenging. Here, we present a protocol ... ...

Abstract	Retinal ganglion cell (RGC) transplantation has the potential to restore vision in optic neuropathy, but donor neuron survival and retinal integration remain challenging. Here, we present a protocol for
MeSH term(s)	Animals ; Cell Survival ; Humans ; Mice ; Optic Nerve ; Optic Nerve Diseases ; Retina ; Retinal Ganglion Cells
Language	English
Publishing date	2022-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101328
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Article ; Online: The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

Zhang, Kevin Y / Johnson, Thomas V

Experimental eye research

2021 Volume 206, Page(s) 108545

Abstract: Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal ... ...

Abstract	Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal interface. While the ILM is essential for normal retinal development, it is dispensable in adulthood. Moreover, the ILM may constitute a significant barrier to emerging ocular therapeutics, such as viral gene therapy or stem cell transplantation. Here we take a neurodevelopmental perspective in examining how retinal neurons, glia, and vasculature interact with individual extracellular matrix constituents at the ILM. In addition, we review evidence that the ILM may impede novel ocular therapies and discuss approaches for achieving retinal parenchymal targeting of gene vectors and cell transplants delivered into the vitreous cavity by manipulating interactions with the ILM.
MeSH term(s)	Basement Membrane/diagnostic imaging ; Extracellular Matrix/metabolism ; Eye Diseases/diagnosis ; Eye Diseases/metabolism ; Eye Diseases/therapy ; Humans ; Retina/diagnostic imaging ; Vitreous Body/diagnostic imaging
Language	English
Publishing date	2021-03-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2021.108545
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Article ; Online: Deletion of Transglutaminase 2 from Mouse Astrocytes Significantly Improves Their Ability to Promote Neurite Outgrowth on an Inhibitory Matrix.

Emerson, Jacen / Delgado, Thomas / Girardi, Peter / Johnson, Gail V W

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Astrocytes are the primary support cells of the central nervous system (CNS) that help maintain the energetic requirements and homeostatic environment of neurons. CNS injury causes astrocytes to take on reactive phenotypes with an altered overall ... ...

Abstract	Astrocytes are the primary support cells of the central nervous system (CNS) that help maintain the energetic requirements and homeostatic environment of neurons. CNS injury causes astrocytes to take on reactive phenotypes with an altered overall function that can range from supportive to harmful for recovering neurons. The characterization of reactive astrocyte populations is a rapidly developing field, and the underlying factors and signaling pathways governing which type of reactive phenotype that astrocytes take on are poorly understood. Our previous studies suggest that transglutaminase 2 (TG2) has an important role in determining the astrocytic response to injury. Selectively deleting TG2 from astrocytes improves functional outcomes after CNS injury and causes widespread changes in gene regulation, which is associated with its nuclear localization. To begin to understand how TG2 impacts astrocytic function, we used a neuron-astrocyte co-culture paradigm to compare the effects of TG2-/- and wild-type (WT) mouse astrocytes on neurite outgrowth and synapse formation. Neurons were grown on a control substrate or an injury-simulating matrix comprised of inhibitory chondroitin sulfate proteoglycans (CSPGs). Compared to WT astrocytes, TG2-/- astrocytes supported neurite outgrowth to a significantly greater extent only on the CSPG matrix, while synapse formation assays showed mixed results depending on the pre- and post-synaptic markers analyzed. We hypothesize that TG2 regulates the supportive functions of astrocytes in injury conditions by modulating gene expression through interactions with transcription factors and transcription complexes. Based on the results of a previous yeast two-hybrid screen for TG2 interactors, we further investigated the interaction of TG2 with Zbtb7a, a ubiquitously expressed transcription factor. Co-immunoprecipitation and colocalization analyses confirmed the interaction of TG2 and Zbtb7a in the nucleus of astrocytes. Overexpression or knockdown of Zbtb7a levels in WT and TG2-/- astrocytes revealed that Zbtb7a robustly influenced astrocytic morphology and the ability of astrocytes to support neuronal outgrowth, which was significantly modulated by the presence of TG2. These findings support our hypothesis that astrocytic TG2 acts as a transcriptional regulator to influence astrocytic function, with greater influence under injury conditions that increase its expression, and Zbtb7a likely contributes to the overall effects observed with astrocytic TG2 deletion.
MeSH term(s)	Animals ; Mice ; Astrocytes/metabolism ; Cell Line, Tumor ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Neurites ; Neuronal Outgrowth ; Protein Glutamine gamma Glutamyltransferase 2 ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Protein Glutamine gamma Glutamyltransferase 2 (EC 2.3.2.13) ; Transcription Factors
Language	English
Publishing date	2023-03-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076058
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Article ; Online: Brodifacoum contamination of synthetic cannabinoid causing unexplained coagulopathy in multiple trauma: A case report.

Thomas, Anthony V / Johnson, Mackenzie L / Tincher, Anna M / Zackariya, Saniya / Khan, Hassaan / Rizvi, Uzma / Thomas, Scott G / Noveroske, Timothy W / Fulkerson, Daniel H / Moore, Ernest E / Walsh, Mark M

Trauma case reports

2024 Volume 51, Page(s) 101007

Abstract: An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated ... ...

Abstract	An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.
Language	English
Publishing date	2024-04-01
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	2835433-3
ISSN	2352-6440 ; 2352-6440
ISSN (online)	2352-6440
ISSN	2352-6440
DOI	10.1016/j.tcr.2024.101007
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Article ; Online: Systemic β-Blockers Do Not Affect Glaucoma Eye Drop Effectiveness.

Johnson, Thomas V / Jampel, Henry D

Ophthalmology

2020 Volume 128, Issue 2, Page(s) 326–328

MeSH term(s)	Administration, Ophthalmic ; Adrenergic beta-Antagonists/therapeutic use ; Antihypertensive Agents/therapeutic use ; Cardiovascular Diseases/drug therapy ; Glaucoma, Open-Angle/drug therapy ; Humans ; Intraocular Pressure/drug effects ; Ophthalmic Solutions
Chemical Substances	Adrenergic beta-Antagonists ; Antihypertensive Agents ; Ophthalmic Solutions
Language	English
Publishing date	2020-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392083-5
ISSN	1549-4713 ; 0161-6420
ISSN (online)	1549-4713
ISSN	0161-6420
DOI	10.1016/j.ophtha.2020.06.062
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Article ; Online: Retina-sparing suprachoroidal intraocular foreign body resulting in cyclodialysis cleft.

Kane, Colin P / Johnson, Thomas V / Sachdeva, Mira M

American journal of ophthalmology case reports

2022 Volume 26, Page(s) 101571

Abstract: Purpose: Suprachoroidal intraocular foreign bodies (IOFBs) are an exceedingly rare manifestation of ocular trauma. Here we present a unique case of a metallic wire tracking from the cornea through the suprachoroidal space, and remarkably sparing the ... ...

Abstract	Purpose: Suprachoroidal intraocular foreign bodies (IOFBs) are an exceedingly rare manifestation of ocular trauma. Here we present a unique case of a metallic wire tracking from the cornea through the suprachoroidal space, and remarkably sparing the retina and lens. The patient attained an excellent visual outcome after management of resultant cyclodialysis cleft. Observations: A 34-year-old male experienced a penetrating IOFB while operating a rotary wire brush. He presented to the emergency department where posterior involvement of the IOFB was confirmed on CT scan. He underwent emergent pars plana vitrectomy, during which the IOFB was found to be located underneath intact retina and choroid on scleral depression. The wire was removed through the entry wound, which was self-sealing. At follow up, intraocular pressure was 3 mmHg with findings of hypotony. A cyclodialysis cleft was confirmed with ultrasound biomicroscopy. Cycloplegic and photocoagulation treatments were attempted, but ultimately direct cyclopexy was performed to successfully repair the cleft. One year after the initial incident, visual acuity is 20/25 and IOP is 17 mmHg. Conclusion and importance: Cyclodialysis cleft is a rare sequela of penetrating ocular injury. Clinicians should consider the presence of a cyclodialysis cleft in the setting of postoperative hypotony and confirm either with gonioscopy or other anterior segment imaging methods. Despite failure of conservative therapies, our patient had an excellent visual outcome following surgical closure of the cleft.
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Case Reports
ISSN	2451-9936
ISSN (online)	2451-9936
DOI	10.1016/j.ajoc.2022.101571
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Article ; Online: Deletion of Transglutaminase 2 from Mouse Astrocytes Significantly Improves Their Ability to Promote Neurite Outgrowth on an Inhibitory Matrix

Jacen Emerson / Thomas Delgado / Peter Girardi / Gail V. W. Johnson

International Journal of Molecular Sciences, Vol 24, Iss 6058, p

2023 Volume 6058

Abstract	Astrocytes are the primary support cells of the central nervous system (CNS) that help maintain the energetic requirements and homeostatic environment of neurons. CNS injury causes astrocytes to take on reactive phenotypes with an altered overall function that can range from supportive to harmful for recovering neurons. The characterization of reactive astrocyte populations is a rapidly developing field, and the underlying factors and signaling pathways governing which type of reactive phenotype that astrocytes take on are poorly understood. Our previous studies suggest that transglutaminase 2 (TG2) has an important role in determining the astrocytic response to injury. Selectively deleting TG2 from astrocytes improves functional outcomes after CNS injury and causes widespread changes in gene regulation, which is associated with its nuclear localization. To begin to understand how TG2 impacts astrocytic function, we used a neuron-astrocyte co-culture paradigm to compare the effects of TG2−/− and wild-type (WT) mouse astrocytes on neurite outgrowth and synapse formation. Neurons were grown on a control substrate or an injury-simulating matrix comprised of inhibitory chondroitin sulfate proteoglycans (CSPGs). Compared to WT astrocytes, TG2−/− astrocytes supported neurite outgrowth to a significantly greater extent only on the CSPG matrix, while synapse formation assays showed mixed results depending on the pre- and post-synaptic markers analyzed. We hypothesize that TG2 regulates the supportive functions of astrocytes in injury conditions by modulating gene expression through interactions with transcription factors and transcription complexes. Based on the results of a previous yeast two-hybrid screen for TG2 interactors, we further investigated the interaction of TG2 with Zbtb7a, a ubiquitously expressed transcription factor. Co-immunoprecipitation and colocalization analyses confirmed the interaction of TG2 and Zbtb7a in the nucleus of astrocytes. Overexpression or knockdown of Zbtb7a levels in WT and TG2−/− ...
Keywords	transglutaminase 2 ; astrocytes ; neurons ; neurite outgrowth ; CNS injury ; Zbtb7a ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Intraocular Pressure Following Prerandomization Glaucoma Medication Washout in the HORIZON and COMPASS Trials.

Johnson, Thomas V / Jampel, Henry D

American journal of ophthalmology

2020 Volume 216, Page(s) 110–120

Abstract: Purpose: To assess the effectiveness of topical ocular hypotensive medications in patients with open-angle glaucoma and to identify factors associated with postwashout intraocular pressure (IOP) elevation.: Design: Secondary analysis of ... ...

Abstract	Purpose: To assess the effectiveness of topical ocular hypotensive medications in patients with open-angle glaucoma and to identify factors associated with postwashout intraocular pressure (IOP) elevation. Design: Secondary analysis of prerandomization data from 2 prospective, multicenter, randomized clinical trials. Methods: Fourteen hundred subjects (1,400 eyes, 781 from the HORIZON study of the Hydrus micro-stent and 619 from the COMPASS study of the Cypass micro-stent) with primary open-angle glaucoma who were using 0-4 classes of topical IOP-lowering medication underwent Goldmann applanation tonometry before and after a protocol-defined washout period. Results: The mean (standard deviation) age was 70.7 (8.0) years and 55.6% were female. The change in IOP following washout for patients using 0 (n = 100), 1 (n = 705), 2 (n = 355), 3 (n = 214), or 4 (n = 26) medications was 0.2 (2.8), 5.7 (3.3), 6.9 (3.7), 8.8 (5.0), and 9.5 (4.1) mm Hg, respectively (P < .001, Kruskal-Wallis test). Postwashout IOP change was similar between the HORIZON and COMPASS cohorts. No difference in postwashout IOP change was detected among individual prostaglandin analogues in patients on monotherapy. A generalized linear model identified the following factors to be associated with greater IOP rise upon medication washout: greater number of glaucoma medications, higher unmedicated IOP, thinner central corneal thickness (CCT), lack of prior selective laser trabeculoplasty (SLT), and male sex. Conclusions: Cessation of glaucoma medications results in a dose-dependent IOP increase in treated open-angle glaucoma patients. Two independent clinical trial cohorts exhibit similar levels of IOP elevation upon washout, using standardized methodology to estimate real-world medication effectiveness. Thicker CCT and history of SLT may predict reduced response to IOP lowering medications.
MeSH term(s)	Administration, Ophthalmic ; Aged ; Aged, 80 and over ; Antihypertensive Agents/therapeutic use ; Female ; Glaucoma Drainage Implants ; Glaucoma, Open-Angle/drug therapy ; Glaucoma, Open-Angle/surgery ; Humans ; Intraocular Pressure/drug effects ; Intraocular Pressure/physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prosthesis Implantation ; Risk Factors ; Single-Blind Method ; Tonometry, Ocular ; Visual Field Tests
Chemical Substances	Antihypertensive Agents ; Ophthalmic Solutions
Language	English
Publishing date	2020-04-11
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80030-2
ISSN	1879-1891 ; 0002-9394
ISSN (online)	1879-1891
ISSN	0002-9394
DOI	10.1016/j.ajo.2020.04.008
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Article ; Online: Retinal Ganglion Cell Transplantation: Approaches for Overcoming Challenges to Functional Integration.

Zhang, Kevin Y / Aguzzi, Erika A / Johnson, Thomas V

Cells

2021 Volume 10, Issue 6

Abstract: As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To ... ...

Abstract	As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To functionally restore vision, lost RGCs must be replaced. Despite tremendous advancements in experimental models of optic neuropathy that have elucidated pathways to induce
MeSH term(s)	Animals ; Humans ; Nerve Regeneration ; Neuroprotection ; Regenerative Medicine/methods ; Retinal Ganglion Cells/cytology ; Retinal Ganglion Cells/transplantation ; Stem Cell Transplantation/methods
Language	English
Publishing date	2021-06-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10061426
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