Vulnerability of dopaminergic amacrine cells and optic nerve myelination to prenatal endotoxin exposure.
OBJECTIVE
Intrauterine infection has been linked to preterm delivery and neurologic injury. The purpose of this study was to investigate the effects of fetal inflammation induced by exposure to endotoxin on the structure and neurochemistry of the retina and optic nerve.


METHODS
The bacterial endotoxin, lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65 of the approximately 147-day gestation period via repeated bolus doses (1 microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10 days after the first LPS exposure.


RESULTS
In the retina, the total number of tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine cells. The total number of myelinated axons in the optic nerve was not different (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in LPS-exposed fetuses.


CONCLUSIONS
Prenatal exposure to repeated doses of endotoxin results in alterations to the retina and optic nerve with specific effects on dopaminergic neurons and myelination, respectively. These findings could have implications for visual function.
Loeliger
Michelle
M
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia. m.loeliger@unimelb.edu.au
Duncan
Jhodie
J
Cock
Megan
M
Harding
Richard
R
Rees
Sandra
S
D025042:Amacrine Cells / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages; D017628:Microglia; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009900:Optic Nerve / Q000196:embryology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011954:Receptors, Dopamine / Q000378:metabolism*; D012756:Sheep / Q000196:embryology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D011954:Receptors, Dopamine; C482199:lipopolysaccharide, E coli O55-B5; D009249:NADP; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase