PIGMENT EPITHELIUM REMOVAL AND TRANSPLANTATION

Project Details

Description

Age-related Macular Degeneration (AMD) is the leading cause of blindness
in persons over age 55 in the United States and Western Europe. In 80-
90% of cases, severe visual loss is caused by the growth of choroidal
neovascular membranes (CNVs) under the RPE and retina. While laser
therapy is the only proven treatment for CNVs a minority of patients are
candidates for treatment, which is complicated by relatively poor visual
outcome and a high rate of recurrent disease. Our desire to carry our
RPE debridement, RPE transplantation, and growth factor treatment studies
arises from the development of a new surgical technique (subretinal
dissection and excision of CNVs) to treat the exudative complications of
AMD. Excised CNVs are associated with overlying RPE and Bruch's membrane
fragments. Thus, a large area of RPE is debrided as a consequence of CNV
removal. We believe removal of RPE limits photoreceptor (and visual)
recovery. We will model CNV-associated RPE removal by mechanically
debriding RPE from Bruch's membrane. We will determine whether RPE
transplantation and/or growth factor therapy reverses these changes.
These experiments may establish a basis for RPE transplantation in humans
following surgical removal of CNVs. The effect of varying the surface
area of debridement on photoreceptor survival centrally will be
described. The time course of retinal degeneration following debridement
will be described. The ability of proliferating RPE to migrate from the
edge into the center of the debrided area and to rescue overlying and/or
adjacent photoreceptors will be assessed. For growth factor studies, the
ability of basic fibroblast growth factor to prevent retinal degeneration
induced by RPE debridement will be assessed. For RPE transplantation,
a suspension of cultured cells is then transplanted over the tapetum.
Transplanted RPE are identified by their pigmentation, and, in some
cases, by fluorescent labels or by a marker gene (pSV GAL). We will
evaluate different vehicles for RPE delivery, determine the number of RPE
cells needed to repopulate a debrided surface, and evaluate homologous
(and perhaps autologous) transplants. The viability of transplants, the
ability of transplants to rescue overlying/neighboring photoreceptors,
and the possibility of transplant proliferation, rejection or the
development of proliferative vitreoretinopathy will be assessed with
light and electron microscopy.
StatusFinished
Effective start/end date3/1/939/30/03

Funding

  • National Institutes of Health: $281,466.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $734,527.00
  • National Institutes of Health
  • National Institutes of Health: $296,818.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $164,270.00

ASJC

  • Medicine(all)

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