The Royal College of Surgeons (RCS) rat is an established animal model used to study human retinal dystrophies. This study investigated whether kidney dysfunction accompanies the eye abnormalities seen in this model. Overnight urine collection procedures were used to measure protein excretion in 2, 12, and 22 month old female pigmented RCS rats and control rats (RDY). Clearance experiments were performed in anesthetized rats to measure glomerular filtration rate (GFR) and renal plasma flow rate (RPF). There was an age-related increase in protein excretion in both RCS and RDY rats, but the protein excretion was significantly higher in the RCS rats at 2 and 22 months of age. Whole kidney GFR and RPF were significantly lower in the 22 month old RCS rats, when compared to age-matched RDY rats. These findings suggest that the RCS rat exhibits both kidney and eye abnormalities. / Department of Physiology and Health Science

[Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.

Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished