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Article ; Online: R. Rand Allingham, M.D. (1953-2018).

Stamer, W Daniel / Ethier, C Ross

2020 Volume 192, Page(s) 107927

Language	English
Publishing date	2020-01-09
Publishing country	England
Document type	Editorial
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2020.107927
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Article ; Online: Development and testing of a metabolic chamber for effluent collection during whole eye perfusions.

De Ieso, Michael L / Kelly, Ruth / Mzyk, Philip / Stamer, W Daniel

Experimental eye research

2023 Volume 236, Page(s) 109652

Abstract: Ocular hypertension is caused by dysregulated outflow resistance regulation by the conventional outflow (CO) pathway. The physiology of the CO pathway can be directly studied during ex vivo ocular perfusions. In addition to measuring outflow resistance ... ...

Abstract	Ocular hypertension is caused by dysregulated outflow resistance regulation by the conventional outflow (CO) pathway. The physiology of the CO pathway can be directly studied during ex vivo ocular perfusions. In addition to measuring outflow resistance generation by the CO tissues, perfusion media that is conditioned by CO pathway cells can be collected upon exiting the eye as effluent. Thus, contents of effluent include factors contributed by upstream cells that report on the (dys)functionality of the outflow tissues. Two methods have been used in the past to monitor effluent contents from perfused eyes, each with their limitations. To overcome these limitations, we designed and printed a metabolic chamber to accommodate eyes of different sizes during perfusions. To test this new chamber, human eyes were perfused for 4 h at constant flow rate of 2.5 μl/min, while pressure was continuously monitored and effluent was collected every hour. Facility was 0.28 ± 0.16 μl/min/mmHg for OD eyes and 0.33 ± 0.11 μl/min/mmHg for OS eyes (n = 3). Effluent samples were protein rich, with protein concentration ranging from 2700 to 10,000 μg/ml for all eyes and timepoints (N = 3). Effluent samples expressed proteins that were actively secreted by the TM and easily detectible including MYOC and MMP2. Taken together, our model provides a reliable method to collect effluent from ex vivo human eyes, while maintaining whole globe integrity.
MeSH term(s)	Humans ; Aqueous Humor/metabolism ; Trabecular Meshwork/metabolism ; Proteins/metabolism ; Glaucoma ; Perfusion
Chemical Substances	Proteins
Language	English
Publishing date	2023-09-16
Publishing country	England
Document type	Journal Article ; 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.2023.109652
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Article: A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Safa, Babak N / Guzmán, Nina Sara Fraticelli / Li, Guorong / Daniel Stamer, W / Feola, Andrew J / Ross Ethier, C

bioRxiv : the preprint server for biology

2024

Abstract: Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intraocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ... ...

Abstract	Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intraocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: 'young' (2-6 months), 'middle-aged' (11-16 months), and 'elderly' (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area to varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs, and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.17.562754
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Article ; Online: ISOPT

Neumann, Ron / Stamer, W Daniel

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

2019 Volume 35, Issue 8, Page(s) 423

MeSH term(s)	Congresses as Topic ; Eye Diseases/drug therapy ; Humans
Language	English
Publishing date	2019-10-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1237021-6
ISSN	1557-7732 ; 1080-7683
ISSN (online)	1557-7732
ISSN	1080-7683
DOI	10.1089/jop.2018.29057.int
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Zs.A 2099: Show issues

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Article ; Online: Artificial Intelligence Models for Cell Type and Subtype Identification Based on Single-Cell RNA Sequencing Data in Vision Science.

Madadi, Yeganeh / Monavarfeshani, Aboozar / Chen, Hao / Stamer, W Daniel / Williams, Robert W / Yousefi, Siamak

IEEE/ACM transactions on computational biology and bioinformatics

2023 Volume 20, Issue 5, Page(s) 2837–2852

Abstract: Single-cell RNA sequencing (scRNA-seq) provides a high throughput, quantitative and unbiased framework for scientists in many research fields to identify and characterize cell types within heterogeneous cell populations from various tissues. However, ... ...

Abstract	Single-cell RNA sequencing (scRNA-seq) provides a high throughput, quantitative and unbiased framework for scientists in many research fields to identify and characterize cell types within heterogeneous cell populations from various tissues. However, scRNA-seq based identification of discrete cell-types is still labor intensive and depends on prior molecular knowledge. Artificial intelligence has provided faster, more accurate, and user-friendly approaches for cell-type identification. In this review, we discuss recent advances in cell-type identification methods using artificial intelligence techniques based on single-cell and single-nucleus RNA sequencing data in vision science. The main purpose of this review paper is to assist vision scientists not only to select suitable datasets for their problems, but also to be aware of the appropriate computational tools to perform their analysis. Developing novel methods for scRNA-seq data analysis remains to be addressed in future studies.
MeSH term(s)	Artificial Intelligence ; Gene Expression Profiling/methods ; Single-Cell Analysis/methods ; Cluster Analysis ; Sequence Analysis, RNA/methods ; RNA/genetics
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1557-9964
ISSN (online)	1557-9964
DOI	10.1109/TCBB.2023.3284795
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Article ; Online: A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Safa, Babak N / Fraticelli Guzmán, Nina Sara / Li, Guorong / Stamer, W Daniel / Feola, Andrew J / Ethier, C Ross

Journal of biomechanical engineering

2024 Volume 146, Issue 8

Abstract: Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ... ...

Abstract	Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: "young" (2-6 months), "middle-aged" (11-16 months), and "elderly" (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area on varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.
MeSH term(s)	Humans ; Aged ; Mice ; Animals ; Aqueous Humor/metabolism ; Intraocular Pressure ; Mice, Inbred C57BL ; Trabecular Meshwork/metabolism ; Glaucoma
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	243094-0
ISSN	1528-8951 ; 0148-0731
ISSN (online)	1528-8951
ISSN	0148-0731
DOI	10.1115/1.4065164
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Zs.B 2672: Show issues

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Article ; Online: Comparison of the extracellular vesicle proteome between glaucoma and non-glaucoma trabecular meshwork cells.

McDonnell, Fiona S / Riddick, Bre'Ida J / Roberts, Haven / Skiba, Nikolai / Stamer, W Daniel

Frontiers in ophthalmology

2023 Volume 3

Abstract: Introduction: Extracellular matrix (ECM) materials accumulate in the trabecular meshwork (TM) tissue of patients with glaucoma, which is associated with a decrease in aqueous humor outflow and therefore an increase in intraocular pressure. To explore a ... ...

Abstract	Introduction: Extracellular matrix (ECM) materials accumulate in the trabecular meshwork (TM) tissue of patients with glaucoma, which is associated with a decrease in aqueous humor outflow and therefore an increase in intraocular pressure. To explore a potential mechanism for ECM regulation in the TM, we purified extracellular vesicles (EVs) from conditioned media of differentiated TM cells in culture isolated from non-glaucomatous and glaucomatous human donor eyes. Methods: EVs were purified using the double cushion ultracentrifugation gradient method. Fractions containing EV markers CD9 and TSG101 were analyzed using nanoparticle tracking analysis to determine their size and concentration. We then determined their proteomic cargo by mass spectrometry and compared protein profiles of EVs between normal and glaucomatous TM cells using PANTHER. Key protein components from EV preparations were validated with Western blotting. Results: Results showed changes in the percentage of ECM proteins associated with EVs from glaucomatous TM cells compared to non-glaucomatous TM cells (5.7% vs 13.1% respectively). Correspondingly, we found that two ECM-related cargo proteins found across all samples, fibronectin and EDIL3 were significantly less abundant in glaucomatous EVs (<0.3 fold change across all groups) compared to non-glaucomatous EVs. Discussion: Overall, these data establish that ECM materials are prominent proteomic cargo in EVs from TM cells, and their binding to EVs is diminished in glaucoma.
Language	English
Publishing date	2023-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	3123828-2
ISSN	2674-0826 ; 2674-0826
ISSN (online)	2674-0826
ISSN	2674-0826
DOI	10.3389/fopht.2023.1257737
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Article ; Online: Estrogen dysregulation, intraocular pressure, and glaucoma risk.

Youngblood, Hannah / Schoenlein, Patricia V / Pasquale, Louis R / Stamer, W Daniel / Liu, Yutao

Experimental eye research

2023 Volume 237, Page(s) 109725

Abstract: Characterized by optic nerve atrophy due to retinal ganglion cell (RGC) death, glaucoma is the leading cause of irreversible blindness worldwide. Of the major risk factors for glaucoma (age, ocular hypertension, and genetics), only elevated intraocular ... ...

Abstract	Characterized by optic nerve atrophy due to retinal ganglion cell (RGC) death, glaucoma is the leading cause of irreversible blindness worldwide. Of the major risk factors for glaucoma (age, ocular hypertension, and genetics), only elevated intraocular pressure (IOP) is modifiable, which is largely regulated by aqueous humor outflow through the trabecular meshwork. Glucocorticoids such as dexamethasone have long been known to elevate IOP and lead to glaucoma. However, several recent studies have reported that steroid hormone estrogen levels inversely correlate with glaucoma risk, and that variants in estrogen signaling genes have been associated with glaucoma. As a result, estrogen dysregulation may contribute to glaucoma pathogenesis, and estrogen signaling may protect against glaucoma. The mechanism for estrogen-related protection against glaucoma is not completely understood but likely involves both regulation of IOP homeostasis and neuroprotection of RGCs. Based upon its known activities, estrogen signaling may promote IOP homeostasis by affecting extracellular matrix turnover, focal adhesion assembly, actin stress fiber formation, mechanosensation, and nitric oxide production. In addition, estrogen receptors in the RGCs may mediate neuroprotective functions. As a result, the estrogen signaling pathway may offer a therapeutic target for both IOP control and neuroprotection. This review examines the evidence for a relationship between estrogen and IOP and explores the possible mechanisms by which estrogen maintains IOP homeostasis.
MeSH term(s)	Humans ; Intraocular Pressure ; Glaucoma ; Trabecular Meshwork/metabolism ; Aqueous Humor/metabolism ; Estrogens/metabolism ; Estrogens/therapeutic use
Chemical Substances	Estrogens
Language	English
Publishing date	2023-11-11
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2023.109725
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Article ; Online: Rare protective variants and glaucoma-relevant cell stressors modulate Angiopoietin-like 7 expression.

Aboobakar, Inas F / Collantes, Edward Ryan A / Hauser, Michael A / Stamer, W Daniel / Wiggs, Janey L

Human molecular genetics

2023 Volume 32, Issue 15, Page(s) 2523–2531

Abstract: Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, a larger variant effect size strongly ... ...

Abstract	Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, a larger variant effect size strongly correlates with in silico predictions of increased protein instability (r = -0.98), suggesting that protective variants lower ANGPTL7 protein levels. Here, we show that missense and nonsense variants cause aggregation of mutant ANGPTL7 protein in the endoplasmic reticulum (ER) and decreased levels of secreted protein in human trabecular meshwork (TM) cells; a lower secreted:intracellular protein ratio strongly correlates with variant effects on intraocular pressure (r = 0.81). Importantly, accumulation of mutant protein in the ER does not increase expression of ER stress proteins in TM cells (P > 0.05 for all variants tested). Cyclic mechanical stress, a glaucoma-relevant physiologic stressor, also significantly lowers ANGPTL7 expression in primary cultures of human Schlemm's canal (SC) cells (-2.4-fold-change, P = 0.01). Collectively, these data suggest that the protective effects of ANGPTL7 variants in POAG stem from lower levels of secreted protein, which may modulate responses to physiologic and pathologic ocular cell stressors. Downregulation of ANGPTL7 expression may therefore serve as a viable preventative and therapeutic strategy for this common, blinding disease.
MeSH term(s)	Humans ; Glaucoma, Open-Angle/pathology ; Glaucoma/metabolism ; Trabecular Meshwork/metabolism ; Intraocular Pressure ; Angiopoietins/genetics ; Angiopoietins/metabolism ; Angiopoietin-like Proteins/genetics ; Angiopoietin-like Proteins/metabolism ; Angiopoietin-Like Protein 7/genetics
Chemical Substances	Angiopoietins ; ANGPTL7 protein, human ; Angiopoietin-like Proteins ; Angiopoietin-Like Protein 7
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddad083
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Article ; Online: The role of microRNAs in glaucoma.

Greene, Karah M / Stamer, W Daniel / Liu, Yutao

Experimental eye research

2021 Volume 215, Page(s) 108909

Abstract: In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a ... ...

Abstract	In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a number of physiological conditions and human diseases, including glaucoma. Numerous miRNAs display differential expression in glaucoma-affected tissues, such as aqueous humor, tears, trabecular meshwork, and retina analyzed from patients and animal models, suggesting their potential involvement in glaucoma pathogenesis. Several studies summarized here have also investigated the challenge of delivering intact miRNAs to target tissues in order to develop miRNA-based glaucoma therapies. We extend these reports by conducting an additional layer of analysis that integrates the interaction between glaucoma-related miRNAs and glaucoma-associated genes. We conclude with a comprehensive discussion of the therapeutic potential of miRNAs, the cellular pathways that link these miRNAs together, and the most promising miRNAs for future glaucoma research.
MeSH term(s)	Animals ; Aqueous Humor/metabolism ; Glaucoma/metabolism ; Humans ; Intraocular Pressure ; MicroRNAs/metabolism ; Trabecular Meshwork/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-12-27
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.2021.108909
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