NeuroToxicology 2002-05-01

A quantitative assessment of TPP-induced delayed neuropathy in the retina and lateral geniculate nucleus of the European ferret (Mustela putorius furo).

Lee Lipsitz, Arthur J Weber, Steven J Bursian, Richard J Aulerich, David T Ramsey, Tanaka Duke

Index: Neurotoxicology 23(1) , 33-42, (2002)

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Abstract

Triphenyl phosphite (TPP) has been examined extensively in our lab to assess its degenerative effects on the visual pathway of the European ferret. Tanaka et al. [Fundam. Appl. ToxicoL 22 (1994) 577; J. Toxicol. Environ. Health 58 (1999) 215] reported an age-related pattern of fiber and cell body degeneration progressing from retinal axons and lateral geniculate nucleus (LGN) neurons to the visual cortex. These studies, however, did not address whether TPP exposure results in retinal ganglion cell (RGC) degeneration, nor did they quantify the degenerative effects in the LGN. The purpose of this study was to quantify the effects of TPP on RGCs and LGN neurons. We administered single subcutaneous injections of TPP (1184 mg/kg) to 13 ferrets for histological analysis. The retinae were examined as whole-mounts and the brains sectioned parasagittally (50 microm). RGC countsfrom matched areas of nasal retina showed significantly fewer (21%) neurons in the TPP-treated ferrets (Sd = 282 +/- 52S.D.; 7d = 284 +/- 12S.D.) compared with control (359 +/- 42S.D.). No significant difference in cell number was found in temporal retina, even though this region contained, on average, 13% fewer ganglion cells in TPP-treated ferrets (Sd = 3344 +/- 44S.D.; 7d = 357 +/- 39S.D. versus control = 394 +/- 72S.D.). The mean soma sizes and RGC cell size distributions for nasal and temporal retinae were not significantly different for any group. LGN neurons were significantly smaller (28%) than control in the TPP-treated ferrets (Sd = 155 microm2 +/- 23S.D.; 7d = 152 microm2 +/- 28S.D. versus control = 214 microm2 +/- 9S.D.). Cell size distributions for LGN neurons were shifted toward smaller cell sizes in both TPP-treated groups compared to control.