The effects of 5-fluorouracil on ocular tissues in vitro and in vivo after controlled release from a multifunctional implant.

Purpose: To evaluate the effects of 5-fluorouracil (5-FU) on ocular cells in vitro and the effects of degradable 5-FU-loaded poly(DL-lactide-co-glycolide; PDLGA) 50:50 implant in the rabbit eye in vivo.

Methods: Cytotoxicity was assessed with a tetrazolium salt WST-1 cell proliferation/viability test and a lactate dehydrogenase (LDH) leakage test in rabbit corneal stromal fibroblasts (SIRCs), bovine corneal endothelial cells (BCECs), human conjunctival epithelial cells (IOBA-NHCs), human retinal pigment epithelial cells (ARPE-19), and human corneal epithelial cells (HCECs). The 5-FU-loaded PDLGA implants were surgically placed in rabbit eyes with a deep sclerectomy technique and the histopathology of the eyes was examined.

Histopathology of the three implanted degradable biopolymers in rabbit eye.

New straightforward applications of new biopolymers are needed in glaucoma surgery. The aim of this study was to compare biocompatibility of three biomaterials in rabbit eyes after deep sclerectomy; a collagen implant (AquaFlow) represented the "gold standard". A blend of 85:15 poly(L-lactide-co-glycolide) and 70:30 poly(L-lactide-co-1,3-trimethylene carbonate) copolymers in a molar ratio of 70:30 (Bio-1 = Inion GTR membrane) and poly(DL-lactide-co-glycolide with molar compositions of 50:50 (Bio-2) and 85:15 (Bio-3) were inserted into rabbits eyes.

VEGFR-1 and -2 regulate inflammation, myocardial angiogenesis, and arteriosclerosis in chronically rejecting cardiac allografts.

Objective: Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts.

Methods And Results: Chronic rejection in mouse cardiac allografts induced primitive myocardial, adventitial, and intimal angiogenesis with endothelial expression of CD31, stem cell marker c-kit, and VEGFR-2.

Angiogenic growth factors in cardiac allograft rejection.

Normal adult vasculature is in a quiescent state. In transplanted hearts, peri- and postoperative ischemic and alloimmune stimuli may be interpreted as inadequate tissue perfusion leading to activation of angiogenic signaling. Although this may have protective functions, improper activation of cardiac allograft endothelial cells and smooth muscle cells may actually result in impaired survival of cardiac allografts.

Inhibition of tumor necrosis factor-alpha attenuates myocardial remodeling in rat cardiac allografts.

Background: Tumor necrosis factor-alpha (TNF-alpha) elicits a wide range of pro-inflammatory activities on target cells and mediates diverse cardiovascular processes ranging from heart failure to atherosclerosis. Recently, we demonstrated that TNF-alpha regulates the platelelet-derived growth factor (PDGF)-A/PDGF-Ralpha activation pathway in rat cardiac allograft arteriosclerosis. The aim of this study was to determine the kinetics and biologic role of TNF-alpha and its receptors, TNF-R1 and TNF-R2, in rat cardiac allografts.