Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model Article Swipe
Eunji Hong
,
Tian Feng
,
C. J. Glynn
,
Sophia Tsekov
,
Sizhe Huang
,
Songlin Zhou
,
Zhigang He
,
Siyuan Rao
,
Qianbin Wang
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.18.576306
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.18.576306
Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable “viscobeads” technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.01.18.576306
- https://www.biorxiv.org/content/biorxiv/early/2024/01/23/2024.01.18.576306.full.pdf
- OA Status
- green
- Cited By
- 4
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391131451
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391131451Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.01.18.576306Digital Object Identifier
- Title
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Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma ModelWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-01-23Full publication date if available
- Authors
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Eunji Hong, Tian Feng, C. J. Glynn, Sophia Tsekov, Sizhe Huang, Songlin Zhou, Zhigang He, Siyuan Rao, Qianbin WangList of authors in order
- Landing page
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https://doi.org/10.1101/2024.01.18.576306Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2024/01/23/2024.01.18.576306.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2024/01/23/2024.01.18.576306.full.pdfDirect OA link when available
- Concepts
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Trabecular meshwork, Glaucoma, Intraocular pressure, Ophthalmology, In vivo, Medicine, Biology, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
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4Total citation count in OpenAlex
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2025: 3, 2024: 1Per-year citation counts (last 5 years)
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58Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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