Chronic placental insufficiency affects retinal development in the guinea pig.
OBJECTIVE
Very low birth weight (VLBW) and fetal growth restriction are associated with increased risks of long-term visual impairments, including alterations to contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. This study was conducted to determine whether chronic placental insufficiency (CPI), sufficient to cause growth restriction, results in neurochemical alterations to retinal interneurons, specifically amacrine and horizontal cell populations near term.


METHODS
CPI was induced just before midgestation (term approximately 67 days of gestation, dg) in guinea pigs through unilateral ligation of the uterine artery. Growth-restricted (GR, n = 32) and control (n = 29) fetuses were euthanized at 60 dg and retinas prepared for analysis of amacrine cell populations by using antibodies to calbindin, calretinin, cholineacetyltransferase (ChAT), gamma-amino-butyric acid (GABA), dopamine beta-hydroxylase (D beta H), tyrosine hydroxylase (TH, dopaminergic), and NADPH-diaphorase histochemistry (nitrergic). Calbindin immunoreactivity (IR) was also used to identify horizontal cells. HPLC was used to assess concentrations of catecholamines and Western blot analysis to detect total TH levels.


RESULTS
In GR compared with control fetuses the total number of TH-IR amacrine (P < 0.02) and calbindin-IR horizontal (P < 0.05) cells was reduced; however, there were no differences in the number of the ChAT, calbindin, calretinin, GABAergic, or nitrergic amacrine cell populations. HPLC revealed a reduction in the concentration of dopamine (P < 0.05) and noradrenaline (P < 0.05), and Western blot analysis revealed a reduction in TH in the retinas of GR compared with control fetuses (P < 0.05).


CONCLUSIONS
CPI results in alterations to specific populations of retinal neurons. Such effects could contribute to visual impairments reported for VLBW children.
Loeliger
Michelle
M
Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia. m.loeliger@unimelb.edu.au
Briscoe
Todd
T
Lambert
Gavin
G
Caddy
Jacinta
J
Rehn
Alexandra
A
Dieni
Sandra
S
Rees
Sandra
S
D025042:Amacrine Cells / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D064032:Calbindin 2; D064026:Calbindins; D002395:Catecholamines / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D007124:Immunoenzyme Techniques; D009252:NADPH Dehydrogenase / Q000378:metabolism; D010927:Placental Insufficiency / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012160:Retina / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D064032:Calbindin 2; D064026:Calbindins; D002395:Catecholamines; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D009252:NADPH Dehydrogenase; D002795:Choline O-Acetyltransferase