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Background
Extracapsular cataract extraction and implantation of intraocular lenses
are being performed at ever increasing rates in the US and in the industrialized
world. In the US, over one million of these procedures are performed each year.
As baby boomers grow older, the incidence of such procedures is expected to rise.
Therefore, there is a great need for replacement of lenses. At the present, most
replacement lenses are made from plastic or glass. These fail to fully replace
the function of the natural lens, and most patients must resort to spectacles
for distance vision. One solution to this problem is to use a lens made of natural
components of a vertebrate lens. Since the only sources for obtaining natural
lens components are from human cadavers or from animals, both of which are expensive
sources, this is not a viable option. Towards this end, investigators have been
studying mechanisms involved in vertebrate lens development.
Description of the
Project
Drs. Lang, Hemmati-Brivanlou and coworkers, studying the complex
process of lens induction, have found that Pax-6, a paired-domain
and a homeodomain containing transcription factor, appears to
act as a master control gene. The role of Pax-6 in lens development
has been defined in a number of systems. In Drosophila, the mutant
called eyeless has a mutation in the fruitfly orthologue of Pax-6.
In humans, Pax-6 heterozygotes develop ocular defects like aniridia
and Peter's anomaly. Using frog embryos, the investigators have
selectively induced vertebrate lenses in ectopic cells by the
administration of Pax-6 encoding nucleic acid. These results suggest
that Pax-6 can direct lens formation without any extraneous factors.
Therefore, the critical events in lens induction may be those
activating and maintaining Pax-6 expression.
To this end, the investigators
have cloned the Pax-6 promoter, and delineated a 350 bp region within it
that can direct the expression of Pax-6 to the lens ectoderm. This DNA segment
is the first known lens-specific transcriptional control element. This highly
conserved lens transcriptional control element could be used to direct the
expression of various genes to the presumptive lens tissue. It could also
be used to isolate transcription factors that bind to this fragment to mediate
lens development by regulating Pax-6 gene expression in ectodermal cells.
Applications
The lens-specific transcriptional control element and Pax-6
could be used to generate in vitro growth of vertebrate replacement
lenses. The development of this technology would be of great value
as it could supply an abundant source of lenses from natural sources
for use in human transplantation. The lens-specific transcriptional
control element of Pax-6 also provides a powerful tool to identify
other transcription factors which may be important in inducing
lens formation.
Patent Status
US patent applications have been filed covering this technology.
For further information
please contact
New York University
Industrial Liaison/Technology Transfer
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189
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