F. Dhawahir-Scala, D. Kent, L. Ma, R. Cosstick, C. Sheridan,
UK
The search for a retinal targeted antiscarring agent
Purpose: De-differentiated retinal pigment epithelium cells (Dif-RPE) are responsible for the development of proliferative vitreoretinopathy (PVR). The aim was the development of a precise targeted drug delivery system, in order to exclusively target and arrest the proliferation of the Dif-RPE as well as to decrease the cytotoxic effects on healthy tissue. Setting: Manchester Royal Eye Hospital and The University of Liverpool, UK. Methods: Dif-RPE as well as PVR membranes express a specific cell surface carbohydrate. A naturally occurring substance derived from the edible mushroom named as Agaricus Bisporus Lectin (ABL), binds specifically to this surface carbohydrate previously mentioned. ABL and an antimetabolite(5 Fluoruracil (5FU)) were conjugated through a series of chemical reactions. Different concentrations of the conjugated product (ABL and 5FU) were tested on an RPE cell line (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. Results: The proliferation assay showed a statistically significant antiproliferative effect of the conjugate (ABL+5FU)when compared to controls.The conjugate had a very low amount of 5FU (0.0012 - 0.0025 mg). There was no antiproliferative effect seen after exposure of ARPE 19 cells to ABL or 5FU used independently at similar concentrations as the ones present in the conjugate. Conclusions: ABL and 5FU can be conjugated through a series of complex chemical reactions. The conjugate achieves a 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.
