Cytotoxic effects of antiproliferative agents on human retinal glial cells in vitro

Proliferative vitreoretinopathy (PVR) is characterized by the formation of cellular membranes on the detached retina and also in the vitreous. Glial cells can be found in epiretinal and subretinal membranes from eyes with PVR, proliferative diabetic retinopathy (PDR), idiopathic macular pucker, uveitis and other diseases affecting the retina. Proliferation and contraction of glial cells appears to play a role in the pathogenesis of PVR. This study is designed to inspect the effectiveness of harringtonine, as well as colchicine, daunomycin and fluorouracil, against cellular proliferation of cultured human retinal glial cells that might be involved in the retinal and/or vitreous proliferation.

Cultures of human retinal glial cells were prepared using the enzyme digesting method. Cells that had been in culture for 2-5 passages were used in this study. Harringtonine (0.063 microg/ml approximately 2.0 microg/ml), colchicines (0.5 microg/ml approximately 16.0 microg/ml), daunomycin (0.1 microg/ml approximately 3.2 microg/ml) and 5-fluorouracil (0.5 microg/ml approximately 16.0 microg/ml) were added to cultures of human retinal glial cells and the proliferation rates of the cells were measured by the MTT method.

Harringtonine at the dosage of 0.063 microg/ml induced suppression of cellular growth, but the changes were not statistically significant (p > 0.05). At a dosage ranging from 0.125 microg/ml to 2.0 microg/ml, harringtonine significantly suppressed cellular growth according to the test (p < 0.01). Likewise, other antiproliferative agents inhibited cellular growth significantly at a dosage from 1.0 microg/ml to 16.0 microg/ml (colchicine), 0.2 microg/ml to 3.2 microg/ml (daunomycin) and 1.0 microg/ml to 16.0 microg/ml (5-fluorouracil), but not at 0.5 microg/ml (colchicine), 0.1 microg/ml (daunomycin) and 0.5 microg/ml (5-fluorouracil). The ID50 were 0.33 microg/ml (harringtonine), 3.11 microg/ml (colchicine), 0.79 microg/ml (daunomycin) and 5.23 microg/ml (5-fluorouracil), respectively.

Harringtonine was extremely effective in inhibiting human retinal glial cell proliferation, like other antiproliferative drugs such as colchicine, daunomycin and 5-fluorouracil. Harringtonine, therefore, may be a candidate for further studies regarding the treatment of experimental PVR.