Prevalence of optic disc haemorrhages in an elderly UK Caucasian population and possible association with reticular pseudodrusen—the Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002–2006)

Aims: To determine disc haemorrhages (DH) prevalence in an elderly UK population-the Bridlington Eye Assessment Project (BEAP).Methods: Thirty-degree (30°) fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy.Results: 3548 participants with photographs in at least one eye. DH were present in 53 subjects (1.49%), increasing from 1.17% (65-69-year age-group) to 2.19% (80-84-year age53 group), p=0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open angle glaucoma (OAG). Two of twelve RE (16.67%) with normal tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty (20) eyes had normal tension glaucoma (NTG), 2 of whom had RPD (10%) (p=0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32 - 19.72) and increasing age (OR 1.05, 95% CI 1.00-1.10, p=0.03). DH was associated with RPD (p=0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or AMD grade.Conclusion: DH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia

Unique Effects of Acute Aripiprazole Treatment on the Dopamine D2 Receptor Downstream cAMP-PKA and Akt-GSK3β Signalling Pathways in Rats

Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt-GSK3β signalling pathways in comparison with a D2R antagonist - haloperidol and a D2R partial agonist - bifeprunox. Rats were injected once with aripiprazole (0.75mg/kg, i.p.), bifeprunox (0.8mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.) or vehicle. Five brain regions - the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3β were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3β in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3β signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R