Selective effects of metabolic inhibitors on retinal cultures

Abstract

Tissue cultures of retinas from young rats, rabbits, mice and chick embryos were treated with metabolic inhibitors in order to determine the sensitivity of the various retinal cell types to these agents. Sulphydryl blocking chemicals, i.e. mercurie compounds, arsenicals, arylating agents, alkylating agents and oxidizing agents, and sodium azide caused selective degeneration of all the rod cells without any apparent damage to the other cell types. A tenfold or more increase of the concentrations of these chemicals resulted in nonspecific damage to all the cell types in the explants. Sodium cyanide, sodium fluoride and other metabolic inhibitors did not reveal any such selective cytotoxic properties. N -Ethyl maleimide was the only sulphydryl inhibitor that did not cause selective rod cell degeneration. Nerve cells, neuroglial cells, cones and pigment epithelial cells in retinal cultures showed about the same sensitivity to the chemicals. The mesenchymal cells were the most resistant to the toxic agents. There was a large increase in the number of phagocytes and mast cells concomitant with exportmentally induced rod cell destruction. Nerve cells, neuroglial cells, and mesenchymal cells from the cerebellum and other tissues, however, did not show any such sensitivity to the metabolic inhibitors. Sulphydryl donors and the antioxidant dl -a-tocopherol protected the rod cells against the selective degeneration induced by the sulphydryl inhibitors. The sensitivity of the rod cells in culture increased during the first 8–10 days and did not change thereafter. Plasma clots and high serum concentrations both interfered with the inhibitors. Histochemical studies revealed changes of enzyme activities shortly after exposure to the inhibitors. At relatively low concentrations, the thiol inhibitors caused selective degeneration of all the rod cells in the retinal cultures; however, the same concentrations of inhibitors produced no effects in living animals. The reasons for this difference, as well as the similarities between experimentally induced rod cell degeneration and the degeneration of rod cells in tisstie cultures of dystrophie retinas, are discussed in the present publication. The most important difference between the latter two types of degeneration was the lack of cellular reaction accompanying rod cell degeneration in explants of dystrophic retinas.