Version 1
: Received: 8 July 2019 / Approved: 10 July 2019 / Online: 10 July 2019 (09:53:49 CEST)
Version 2
: Received: 27 April 2020 / Approved: 28 April 2020 / Online: 28 April 2020 (10:42:13 CEST)
Version 3
: Received: 7 December 2020 / Approved: 8 December 2020 / Online: 8 December 2020 (10:09:17 CET)
Waxman, S., Ralitsa Loewen and Nils A. Loewen. 2019 "Tissue-Engineered Anterior Segment Eye Cultures Display an Intraocular Pressure Homeostatic Response" Preprints. https://doi.org/10.20944/preprints201907.0142.v1
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.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
