Submitted:
08 July 2019
Posted:
10 July 2019
Read the latest preprint version here
Abstract
Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye's anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM), an extracellular matrix (ECM)-rich tissue at the entrance of the eye's drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered (TE) anterior segment eye culture model. We hypothesized that repopulation of decellularized TM ECM with non-native TM cells could restore intraocular pressure (IOP) homeostatic ability. Decellularized porcine anterior segment scaffolds demonstrated complete removal of cells, significant reduction of DNA content, and well-preserved ECM ultrastructure. Seeded cells localized to the TM region (p < 0.001) and progressively infiltrated meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After perfusion rate increase challenge, TE cultures maintained healthy IOPs through regulation of outflow resistance (reseeded = 16.53 ± 0.89, decellularized = 35.23 ± 2.20 mmHg, p < 0.0001). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. TE organs demonstrated physiological similarities to native tissues and may reduce the need for scarce donor globes in outflow research.
Keywords:
glaucoma
; tissue engineering
; trabecular meshwork
; outflow facility
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