Different neuronal toxicity of single-chain ribosome-inactivating proteins on the rat retina

ObjectiveTo investigate the neurotoxicity of two structurally similar single chains of ribosome-inactivating proteins (RIPs): trichosanthin (TCS) and ricin A chain (RTA).MethodsTCS, RTA and Ricinus communis agglutinin (RCA, a multi-chain RIP for comparison) were separately injected into rat eyes. Saline was used as control. The data on cell counts, retinal thickness and histopathological scores were collected, and the TUNEL method (terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling) was used to study the mode of cell death.ResultsTCS caused distinct retinal changes at 1 nmol. Its toxic effects were most pronounced on the cells of the outer nuclear layer, less so on those of the inner nuclear layer, and little on the ganglion cells. Apoptosis was the predominant type of cell death induced by TCS. In contrast, RTA and RCA, both at 0.01 nmol, brought about acute retinal inflammation and necrosis.ConclusionTCS can eliminate specific retinal cells by apoptosis, while RTA and RCA cause retinitis. The B chain of type II RIPs is not obligatory for their neurotoxicity. The RIPs may be useful for creating retinal models and TCS may be useful for the chemical treatment of retinoblastoma.