In vitro inhibition of ocular cell proliferation with ara-C: blockage of the antiproliferative effect with 2'-deoxycytidine.

Cytosine arabinoside (ara-C), a cell cycle-phase specific antimetabolite, was tested in a tissue culture model of human scleral fibroblasts (HSCF), and human retinal pigmented epithelium cells (HRPE), to investigate possible applications in the modulation of wound healing after glaucoma filtering surgery and in the postoperative management of proliferative vitreoretinopathy. Cell proliferation after a 72 hr incubation in the presence of ara-C was inhibited to 50% of the control growth rate (ID50) with calculated doses of 60 ng/ml in HSCF and 4 and 5 ng/ml in HRPE cultures. 2'-deoxycytidine, a competitive inhibitor of ara-C action, completely eliminated the cell growth retardation of both cell types produced by ara-C after 72 hr incubation.

Fluorouracil (5-FU) and cytarabine (ara-C) inhibition of corneal epithelial cell and conjunctival fibroblast proliferation.

We evaluated the antiproliferative properties of fluorouracil (5-FU) and cytarabine (ara-C) in a tissue culture model of rabbit corneal epithelial cells and conjunctival fibroblasts. Cells were treated with fluorouracil or cytarabine for five days. Corneal epithelial cell proliferation was inhibited to 50% of control proliferation by 0.6 mg/L of fluorouracil or 30 micrograms/L of cytarabine. Proliferation of conjunctival fibroblasts was inhibited to 50% of control by 0.5 mg/L of fluorouracil or 50 micrograms/L of cytarabine. The antiproliferative effect of 10 mg/L of fluorouracil was not blocked by thymidine. The inhibition of proliferation produced by 100 or 1,000 micrograms/L of cytarabine was blocked by 2'-deoxycytidine at concentrations of 10(-5) M and 10(-4) M, respectively. The antiproliferative effects of fluorouracil and cytarabine appear similar for both cell types. Blockage of cytarabine-related ocular toxic effects may be possible with 2'-deoxycytidine.

Transport of fluorescein in the ocular posterior segment in retinitis pigmentosa.

The function of the blood-retinal barrier was assessed by vitreous fluorophotometry in 12 patients with various genetic types of retinitis pigmentosa and in 11 normal subjects. The measurements were corrected to minimize the effect of artifacts. We evaluated the inward penetration of fluorescein sodium across the blood-retinal barrier and determined the outward permeability coefficient for fluorescein by interpreting the data with a pharmacokinetic computer model. Patients with retinitis pigmentosa had increased inward permeability and decreased outward permeability to fluorescein in comparison with values of normal subjects.

The effect of beta irradiation on monkey Tenon's capsule fibroblasts in tissue culture.

Fibroblast proliferation with subsequent bleb scarring is a major cause of filtering surgery failure. To investigate possible antiproliferative effects of beta radiation, owl monkey Tenon's capsule fibroblasts in tissue culture were irradiated to doses of 30, 100, 300, 1,000, and 3,000 rads with a linear accelerator and to doses of 95,285, and 950 rads with a Strontium-90 applicator. The irradiated cell proliferation expressed as the percentage of the non-irradiated control growth on the third and seventh days, respectively, after beta irradiation was: 97% and 96% after 30 rads; 72% and 90% after 100 rads; 48% and 44% after 300 rads; 39% and 14% after 1,000 rads; and 39% and 14% after 3,000 rads. Similar effects on cell proliferation were observed with the Strontium-90 applicator. The inhibitory effect of beta irradiation on fibroblast proliferation in tissue culture suggests that beta irradiation after filtering surgery may reduce postoperative bleb scarring.

Trifluorothymidine and 5-fluorouracil: antiproliferative activity in tissue culture.

The antiproliferative activity of trifluorothymidine (F3TDR) and 5-fluorouracil (5-FU), two cell-cycle-phase-specific antimetabolites, was compared in a tissue culture model of human scleral fibroblasts and rabbit corneal epithelial cells. The mean concentrations required to inhibit human scleral fibroblast proliferation to 50% of the control rate (ID50) after 5 days of exposure were 8.50 micrograms/mL for F3TDR and 0.43 microgram/mL for 5-FU. The corresponding ID50 levels for rabbit corneal epithelial cells were 0.24 microgram/mL and 0.42 microgram/mL. The ID50 of F3TDR was significantly higher than that of 5-FU in human scleral fibroblasts (p less than 0.001) but not in rabbit corneal epithelial cells. F3TDR appears to have no clinical advantage over 5-FU in minimizing corneal epithelial toxicity when given to prevent fibroblast proliferation after glaucoma filtering surgery.