May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
"Smart" Targeting of Antiscarring Agents in an in vitro Model of Retinal Wound Healing
Author Affiliations & Notes
  • F.E. Dhawahir–Scala
    Manchester Royal Eye Hospital and The University of Liverpool, Manchester and Liverpool, United Kingdom
  • L. Ma
    Department of Chemistry,
    The University of Liverpool, Liverpool, United Kingdom
  • D. Wong
    St Paul's Eye Unit and The University of Liverpool, Liverpool, United Kingdom
  • S. Roberts
    Department of Chemistry,
    The University of Liverpool, Liverpool, United Kingdom
  • D. Kent
    Eye Service, Aut Even Hospital and The University of Liverpool, Kilkenny and Liverpool, Ireland
  • C. Sheridan
    The University of Liverpool, Liverpool, United Kingdom
  • Footnotes
    Commercial Relationships  F.E. Dhawahir–Scala, None; L. Ma, None; D. Wong, None; S. Roberts, None; D. Kent, None; C. Sheridan, None.
  • Footnotes
    Support  British Council For Prevention of Blindnes
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3063. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      F.E. Dhawahir–Scala, L. Ma, D. Wong, S. Roberts, D. Kent, C. Sheridan; "Smart" Targeting of Antiscarring Agents in an in vitro Model of Retinal Wound Healing . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3063.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose: Current treatments available for Proliferative vitreoretinopathy (PVR) have a modest benefit or are toxic in the therapeutic range. Blocking or modifying the action of de–differentiated Retinal Pigment Epithelial cells (RPE), responsible for PVR formation could enhance the overall prognosis of this condition. De–differentiated RPE cells as well as PVR membranes express a specific cell surface carbohydrate. A naturally occurring substance derived from the edible mushroom, the Agaricus Bisporus Lectin (ABL), binds specifically to this surface carbohydrate. The aim of the present study was the development of a precise targeted drug delivery system, specifically the conjugation of ABL with 5–Fluorouracil (5FU), in order to exclusively target and arrest the proliferation of the de–differentiated RPE cells as well as to decrease the cytotoxic effects on other cells that would occur if 5FU was applied independently. Methods: ABL and 5FU were conjugated through a series of chemical reactions. Different concentrations of the conjugated product (ABL and 5FU), non–conjugated ABL and 5FU alone were tested on ARPE19 cells. The exposure time was 30 minutes. The antiproliferative effect on days 1, 3, 7 and 14 was compared using A Non–Radioactive Cell proliferation assay. Controls consisted of the addition of Asialofetuin (ASF), a substance that blocks the action of ABL as well as untreated cells. Results: The proliferation assay showed a statistically significant antiproliferative effect of the conjugate(ABL+5FU) and the 5FU alone at the different time points when compared to the controls. The non–conjugated ABL showed no antiproliferative effect after 30 minutes of exposure. The addition of ASF to the conjugate blocked the antiproliferative effect, indicating that the action of the conjugate is due to the additive effect of ABL with 5FU and not of 5FU alone. Conclusions: The conjugation of ABL and 5FU is achievable through a series of complex chemical reactions. The Conjugate caused a statistically significant antiproliferative effect In Vitro. Future studies will evaluate the effects of the conjugate on other wound healing processes such as migration, adhesion and contraction.

Keywords: retinal detachment • proliferative vitreoretinopathy • vitreoretinal surgery 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×