Project: Research project

Project Details


The corneal epithelium is the main protective barrier for the cornea, and
complete restoration of the corneal epithelium following trauma or surgery
is essential for the restitution of normal visual function. The
mechanism(s) and factors responsible for the maintenance and repair of the
corneal epithelium are unclear. We have discovered that an endogenous
opioid system (EOS) modulates rabbit corneal epithelial explant outgrowth,
re-epithelialization in culture and in vivo, and homeostasis. Moreover,
both the opioid growth factor (OGF), [Met/5]-enkephalin, and its receptor,
zeta, are present in the basal and suprabasal cells of the corneal
epithelium of humans and animals. OGF is a native, tonically active,
inhibitory growth factor that is targeted to growth-related events.
Blockage of OGF action using opioid antagonists such as naltrexone (NTX),
dramatically stimulates the proliferation and migration of corneal
epithelial cells in explants, re-epithelialization in organ culture and in
vivo, and DNA synthesis of epithelial and limbal cells. This grant
explores the hypothesis that an EOS plays a role in the maintenance and
restitution of the corneal epithelium. Specific aims include: (1) Define
the presence and location of OGF, mRNA for OGF hormone (preproenkephalin),
zeta receptor, and OGF binding sites in the epithelium, limbus, and
conjunctiva of normal cornea. (2) Examine the presence, response, and
function of the EOS in rabbit cornea in vivo during injury and repair.
The relationship of EOS to cell proliferation, migration, and
differentiation, and re-epithelialization and healing, will be
established. Paradigms using excess OGF and blockade of OGF-receptor
interaction will be employed to understand EOS function. (3) Elucidate the
influence of EOS on homeostasis of rabbit cornea. (4) Study the influence
of EOS in human corneal epithelium on cell proliferation, migration, and
differentiation, as well as cell/tissue organization, utilizing explants.
(5) Ascertain the biology of EOS in human corneal epithelium, limbus, and
conjunctiva during maintenance, injury, and re-epithelialization using an
organ culture model. These studies are part of a long-range program
directed towards understanding the pathogenesis and treatment of corneal
diseases, particularly disorders of the corneal epithelium.
Effective start/end date2/1/961/31/02


  • National Eye Institute


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