3D neuronal innervated corneal tissue model
Abstract: The cornea
is the outermost layer of human eye and is an important part of the ocular light path.
The cornea is medically significant as corneal diseases account for 25% of blindness in
the world population. Dense neuronal innervation provides vital functions and a
protective role for the cornea including initiation of eye blinking. In addition to
neuronal innervation, aligned ECM ... read moreand stromal cell distribution maintain the
transparency of cornea, while the multilayer epithelium forms an important barrier to
protect ocular tissue. Despite the essential functions of these different structures,
the interactions between nerve and corneal tissue are not clear. Current research
methods are limited to in vivo rabbits, mice and pigs models which do not represent the
human corneal anatomy and physiology. The goal of this research was to establish an in
vitro tissue model to mimic the biological and mechanical environment of the cornea,
using human cells. This in vitro tissue model can be used to study the physiology and
pathology of the human cornea. In this work, a corneal tissue model containing
epithelium and stroma with neuronal innervation was established, using silk protein as
the scaffolding material to mimic the architecture of the cornea. This tissue model
provided aligned growth of stromal cells, multiple layers of epithelial cells and
innervation. Interactions between neurons and corneal cells were investigated in static
culture first. Next, a dynamic culture system, that provides intraocular pressure and
tear flow, was developed to study the impact of the physical environment on in vitro
corneal tissue and nerves. Last, capsaicin nociceptive stimulation was introduced in the
culture to study the impact on the corneal tissue and to establish functionality of the
tissue model. This tissue model and dynamic culture system would benefit drug screening,
testing of implant materials, cornea disease diagnose and related fields. Further, this
tissue system can be used to replace animal models in pre-clinical test for
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Qiaobing Xu, James Funderbrugh, and Kenneth Kenyon.
Keyword: Biomedical engineering.read less
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