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Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model
Karen Y Torrejon1, Ellen L Papke1, Justin R Halman1
1Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
Biotechnology and Bioengineering
|November 29, 2015
Summary
Researchers developed a 3D human trabecular meshwork (HTM) model to study glaucoma. This model mimics steroid-induced glaucoma, showing potential for discovering new therapeutic targets for intraocular pressure (IOP) regulation.
Area of Science:
- Biomedical Engineering
- Ophthalmology
- Glaucoma Research
Background:
- Intraocular pressure (IOP) regulation is crucial for glaucoma management.
- Aqueous humor outflow through the human trabecular meshwork (HTM) is key to IOP control.
- Current therapeutics targeting HTM for IOP modulation are limited, necessitating advanced in vitro models.
Purpose of the Study:
- To engineer a novel 3D HTM model for studying outflow physiology and glaucoma pathology.
- To create an in vitro model that replicates key features of steroid-induced glaucoma.
- To investigate the potential of targeting HTM for developing new glaucoma therapeutics.
Main Methods:
- Development of a 3D HTM model enabling outflow regulation.
- Induction of a fibrotic state in the HTM model using pharmacologic steroids.
- Characterization of the model for HTM marker expression, extracellular matrix (ECM) production, phagocytic activity, and outflow resistance.
- Assessment of the effect of a ROCK inhibitor on steroid-induced ECM alterations.
Main Results:
- The engineered 3D HTM model successfully mimicked glaucomatous HTM characteristics, including fibrotic changes.
- Steroid-induced glaucoma features such as ECM overproduction, impaired phagocytosis, and outflow resistance were observed.
- The model demonstrated that steroid-induced ECM alterations could be modulated by a ROCK inhibitor.
Conclusions:
- A novel in vitro 3D HTM disease model was successfully developed.
- This model facilitates physiological and pathological studies of aqueous humor outflow regulation.
- The model aids in understanding steroid-induced glaucoma and accelerates the discovery of therapeutic targets for IOP management.
