Purpose

Diabetes appears to induce a visual cycle defect because rod dysfunction is correctable with systemic treatment of the visual cycle chromophore 11-cis-retinaldehyde. However, later studies have found no evidence for visual cycle impairment. Here, we further examined whether photoreceptor dysfunction is corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor dysfunction in diabetes, the hypothesis that exogenous visual chromophores have antioxidant activity in the retina of diabetic mice in vivo was tested.

Methods

Rod function in 2-month-old diabetic mice was evaluated using transretinal electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic tracking was used to evaluate cone-based visual performance. Retinal production of superoxide free radicals, generated mostly in rod cells, was biochemically measured with lucigenin. Diabetic mice were systemically treated with a single injection of either 11-cis-retinaldehyde, 9-cis-retinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde).

Results

Consistent with previous reports, diabetes significantly reduced (1) dark-adapted rod photo responses (transretinal recording) by ∼18%, (2) rod-dominated light-stimulated SRS expansion (ADC MRI) by ∼21%, and (3) cone-dominated contrast sensitivity (using optokinetic tracking [OKT]) by ∼30%. Both 11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of photoreceptor dysfunction. Higher-than-normal retinal superoxide production in diabetes by ∼55% was also significantly corrected following treatment with 11-cis-retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde.

Conclusions

Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism.

Background

In patients with heart disease, the presence of a fragmented QRS complex (fQRS) on the surface electrocardiogram (ECG) is associated with an increased risk of mortality. We sought to evaluate the prevalence and location of fQRS before and after left ventricular assist device (LVAD) implantation and any associated risk of mortality.

Methods and results

Twelve-lead surface ECGs before (pre-LVAD, n = 98) and after (early [< 7 days], n = 96, and late [≥ 30 days], n = 85, post-LVAD) LVAD implantation were evaluated for fQRS. Mortality data were gathered via review of medical records. The prevalence of fQRS increased significantly following LVAD implantation on early post-LVAD ECGs (31% to 47%, p < 0.01). Patients with fQRS in the anterior territory (precordial leads V1 to V5) on late post-LVAD ECGs had decreased survival or survival to cardiac transplantation over a 30 month follow-up period compared with patients who did not exhibit anterior fQRS (30% and 59%, respectively, p < 0.01).

Conclusions

The prevalence of fragmented QRS on 12-lead ECG increases significantly in the anterior territory following LVAD implantation and is associated with decreased survival.