Gene Gun Technology, Opioids, and Corneal Diseases

Project: Research project

Project Details

Description

DESCRIPTION: (Applicant's Abstract) The corneal epithelium modulates fluid
transport for normal stromal hydration and corneal transparency, and serves as
an anatomical and physiological barrier against ocular infection. This
epithelium is in a constant state of renewal, and injury to this epithelium
requires prompt resurfacing in order to re-establish visual function. Tools to
achieve research and clinical applications to corneal diseases at the molecular
level offer exciting avenues for advancement, but are stymied by the need for
manipulating gene activity. Progress has been made in gene therapy through the
development of a particle-mediated gene transfer delivery system (gene gun), a
technique shown to be a rapid, highly efficient, and nontoxic method for
transfection of genes both in vivo and in vitro. In this grant we propose to
establish the gene gun as a valuable research tool in corneal epithelial
biology, obtain preliminary information for the efficacy of the gene gun as a
device for clinical treatment, and document the importance of the interaction
of a native inhibitory peptide, opioid growth factor (OGF) with its receptor
(OGFr) at the molecular level as a system regulating the homeostasis and
healing of the ocular surface epithelium in humans and animals. The specific
aims include: 1. Determine the importance of OGF-OGFr interfacing on
maintenance of rat corneal epithelium by examining the consequences of
molecular perturbation of OGF receptor gene and protein activity. 2. Define the
role of an endogenous opioid system related to wound healing of the rat corneal
epithelium following genetic alteration of the OGF receptor gene and protein
expression in rat. 3. Ascertain the significance of OGF and OGFr function
during wound healing of the human corneal epithelium using organ culture of
tissues genetically modified to yield an excess or deficit of OGF receptor.
Information derived from these studies will contribute to a breakthrough
understanding of gene delivery systems to the corneal surface. Moreover, these
investigations will simultaneously acquire invaluable knowledge about the
molecular basis by which an endogenous opioid system relates to corneal
epithelial homeostasis, and the restoration of corneal integrity following
injury. Ultimately, such data can be employed to design molecular strategies to
remedy visual dysfunction.
StatusFinished
Effective start/end date8/1/017/31/02

Funding

  • National Eye Institute: $132,805.00

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