Glucocorticoid enhances the neurotoxic actions of quinolinic acid in the striatum in a cell-specific manner.

This study demonstrates that corticosterone can exacerbate the damaging effects of infused quinolinic acid (QA) on the dorsal striatum. Adult adrenalectomised male rats were pretreated subcutaneously with graded doses of corticosterone (0, 0.5, 2, 5, 20 and 40 mg/kg/day) for 2 days and then received a unilateral infusion of QA (45 nmol) (under Isoflurane/N2O anaesthesia) into the dorsal striatum. A control infusion (vehicle) was made into the striatum on the other side. Corticosterone treatment was continued and they were killed 7 days later. Plasma corticosterone was measured by radioimmunoassay, and thymus weights were used as an integrated measure of glucocorticoid activity. Lesion volumes were measured on neuronal nuclei stained sections, dopamine and cyclic AMP-regulated phosphoprotein 32 (DARRP-32) was used to assess medium spiny neurone survival, NADPH-diaphorase histochemistry to assess medium aspiny neurones and, finally, choline acetyltransferase to assess large aspiny neurones. Adrenalectomised rats showed smaller lesions than control (sham-operated) rats, suggesting significant protection. Increasing doses of corticosterone resulted in larger lesions up to an apparent ceiling effect at higher doses; there was no evidence of a U-shaped dose-response. There was a differential effect of both QA and corticosterone on the cell populations of the striatum. Medium spiny neurones were most vulnerable to the effects of QA and to the exacerbating actions of corticosterone. Medium aspiny neurones were equally vulnerable to QA but corticosterone had no additional effect. Large aspiny neurones were relatively less sensitive to QA and there was no additional action of administered corticosterone. These results show that corticosterone has a selective neuroendangering action within the striatum, but there is no evidence for a protective action of glucocorticoids at lower doses.

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom.

AIMS/PURPOSE: To determine the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in men aged 65-83 years living in the Speedwell region of Bristol, United Kingdom and identify modifiable risk factors. METHODS: A total of 2348 men recruited to the Speedwell prospective cohort study in 1979 were followed up in 1997 with an eye questionnaire and had retinal photographs that were assessed using the International Classification System for ARM. RESULTS: In all, 934 men (66.8% response rate) attended with a mean of 17.9 years (15.3-20.6 years) follow-up. Early ARM (grades 2-3) was found in 9.2% (95% confidence interval (CI) 7.4%, 11.4%) and late age-related maculopathy (grade 4, AMD) in 0.5% (95% CI 0.2%, 1.2%). The risk of ARM (grades 2-4) was increased with raised C-reactive protein and consumption of lard and solid fats, whereas triglyceride levels were associated with a lower risk. The latter were confirmed in multivariable analyses and in addition, haemodynamic measures also predicted risk (eg mean arterial pressure odds ratio (OR) per z-score 1.37, 95% CI 1.04, 1.79). CONCLUSIONS: In a representative cohort of men aged 65-83 from Bristol, United Kingdom, many had macular changes that put them at higher risk of developing AMD. Various modifiable exposures were associated with an increased risk ARM/AMD. Opportunities for screening and undertaking secondary prevention interventions need to be explored to prevent progression of the disease and blindness.