Analysis of the cellular reactions to a minimal injury of the
cornea in the living mouse.
The long term goal of the project is to better understand the corneal
wound healing at a cellular level, which is important in the proper
healing of surgical incisions and laser ablations made in the course of
Most effort is applied to the investigation of the movement and
morphological changes of individual cells in the corneal stroma of the
living mouse. These cells are observed under a confocal microscope or a fluorescence microscope,
and their movements are analyzed by time-lapse digital video microscopy
and subsequent image processing. The mechanisms of cell death,
activation and repopulation after a mild injury, are also characterized.
Both the invading inflammatory cells and the resident stromal
keratocytes are tracked to study their behavior.
In addition, in vivo microscopy is employed to investigate the early
phase of the neovascularization in the mouse cornea after chemical
cauterization, with emphasis on the vascular sprouting and the capillary
Study of tear film components that are cytotoxic to corneal stromal
We have demonstrated previously
that the mouse tears contain factors
that are cytotoxic to the corneal stromal cells but not to the corneal
epithelial cells. The molecular identity, the source, and the mechanism
of action of the tear factors are being investigated. Also, an effort is
put forward to reproduce these observations in humans, and then to
examine the possibility that the cytotoxic tear factors may be involved
in the reconstruction of the corneal stromal tissue after injury or
Pharmacokinetics of drug penetration and delivery in the
posterior segment of the eye.
The kinetics of drugs in the vitreous cavity of the human and rabbit eye
have been modeled by the FEM technique in conjunction with Peter Pinsky
and Deepak Datye of Stanford Engneering Dept.
The rates of loss of fluorescein and fluorescein glucuronide from the human
vitreous cavity are being studied in order to test the prediction of the
A technique for determining how much
drug penetrates from the tear film to the retina is being developed. This
quantity is expected to be very small and special care has to be taken
to avoid contamination that could occur during tissue separation.
In addition, the literature concerning the kinetics of drugs in the
vitreous cavity of the human eye has been extensively reviewed. Some
issues concerning the influence of binding on kinetics will be followed
up with fluorescent tracers in the mouse.
Flow in the vitreous.
The flow pathways in the vitreous body and how they are affected by the
structure of the gel will be examined by MRI techniques. This will be
carried out in collaboration with Dr. Truman Brown, director of the
imaging division of the Columbia University Biomedical Engineering Dept