Different neuronal toxicity of single-chain ribosome-inactivating proteins on the rat retina.
OBJECTIVE
To investigate the neurotoxicity of two structurally similar single chains of ribosome-inactivating proteins (RIPs): trichosanthin (TCS) and ricin A chain (RTA).


METHODS
TCS, 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.


RESULTS
TCS 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.


CONCLUSIONS
TCS 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.
Sha
Ou
O
Department of Anatomy, Basic Medical Sciences Building, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. shaou@cuhk.edu.hk
Kwong
Wing Hang
WH
Pang Cho
Eric Yu
EY
Wai Yew
David Tai
DT
Ng
Tzi Bun
TB
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D009474:Neurons / Q000187:drug effects*; D037121:Plant Lectins / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology* / Q000187:drug effects*; D012276:Ricin / Q000737:chemistry / Q000633:toxicity*; D015978:Trichosanthin / Q000737:chemistry / Q000633:toxicity*
D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; D015978:Trichosanthin; D012276:Ricin