Pharmacokinetics and metabolism in mouse retina of bis-allylic deuterated docosahexaenoic acid (D-DHA), a new dry AMD drug candidate.

Docosahexaenoic acid (DHA; 22:6n-3) rich photoreceptors function in a highly oxidizing microenvironment. Lipid peroxidation and inflammation contribute to initiation and progression of eye diseases including age-related macular degeneration (AMD). Deuteration of DHA at the bis-allylic positions (D-DHA) increases its resilience to oxidative damage in vitro. We studied the pharmacokinetics of dietary D-DHA as a therapy for replacing natural retinal DHA in vivo. Mice were fed 0.5% D-DHA for 77 days then switched to natural DHA (H-DHA) for 74 days. Tissue were harvested for analyses at various time points. D-DHA substitution levels were 75%-80% in the CNS and above 90% in all other tissues by day 77. D-DHA accretion was rapid in plasma and liver (t1/2a ∼2.8 d), followed by heart and red blood cells (t1/2a ∼8.5 d), then ocular tissues (choroid-RPE, neural retina, and optic nerve with t1/2a of 10.1, 23.4, and 26.3 days, respectively), while CNS accretion was slowest (t1/2a of 29.0-44.3 days). D-DHA elimination rates were comparable to, or slower than, accretion rates except for optic nerve. Retina had very long chain D-PUFA (D-VLC-PUFA) with 5 and 6 double bonds up to C36, as well as D-EPA and D-DPA derived metabolically from D-DHA. The neural retina and optic nerve reached the therapeutic target window (20%-50%) in 2-4 weeks. Biosynthesis of D-VLC-PUFA is consistent with normal metabolism. D-DHA crosses the blood-retina-barrier, enters visually active tissues, and is metabolized as its natural DHA parent where, as shown previously (Liu et al., 2022), it protects against lipid peroxidation.

Deuterated docosahexaenoic acid protects against oxidative stress and geographic atrophy-like retinal degeneration in a mouse model with iron overload.

Oxidative stress plays a central role in age-related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes. Oxidation of DHA produces toxic oxidation products including carboxyethylpyrrole (CEP) adducts, which are increased in the retinas of AMD patients. In this study, we hypothesized that deuterium substitution on the bis-allylic sites of DHA in photoreceptor membranes could prevent iron-induced retinal degeneration by inhibiting oxidative stress and lipid peroxidation. Mice were fed with either DHA deuterated at the oxidation-prone positions (D-DHA) or control natural DHA and then given an intravitreal injection of iron or control saline. Orally administered D-DHA caused a dose-dependent increase in D-DHA levels in the neural retina and retinal pigment epithelium (RPE) as measured by mass spectrometry. At 1 week after iron injection, D-DHA provided nearly complete protection against iron-induced retinal autofluorescence and retinal degeneration, as determined by in vivo imaging, electroretinography, and histology. Iron injection resulted in carboxyethylpyrrole conjugate immunoreactivity in photoreceptors and RPE in mice fed with natural DHA but not D-DHA. Quantitative PCR results were consistent with iron-induced oxidative stress, inflammation, and retinal cell death in mice fed with natural DHA but not D-DHA. Taken together, our findings suggest that DHA oxidation is central to the pathogenesis of iron-induced retinal degeneration. They also provide preclinical evidence that dosing with D-DHA could be a viable therapeutic strategy for retinal diseases involving oxidative stress.

Using an educational mobile application to teach students to take vital signs.

BACKGROUND: The utilization of smartphone applications in educational settings, specifically in the field of nursing, has grown increasingly popular. To date, there have been few, if any, smartphone applications dedicated specifically to the teaching of vital signs. The Clinic Vitals app was designed to be an acceptable substitute for in-person vital signs instruction. OBJECTIVES: The objective of this study was to show the utility of the Clinic Vitals app as a pedagogical tool in comparison to in-person nursing educational instruction. DESIGN: A crossover design was employed within collegiate nursing educational sessions to determine if Clinic Vitals was an equivalent alternative to traditional vital sign teaching methods. PARTICIPANTS: Participants were first-year nursing students from six different lab sessions within the same undergraduate university. METHODS: Students with little to no vital sign experience were given instruction via the Clinic Vitals mobile application or traditional learning. After the learning session, students were given skills assessments. After one week, students were given the opposite method of instruction followed by skills assessments. RESULTS: Results showed that no significant difference was found between the two groups based on skills assessments. Mobile application and in-person instruction teaching methods produced a similar level of competency in students learning to take vital signs. CONCLUSIONS: The utility of being able to access the application's videos and instructional articles at any time and anywhere that there is an internet connection would make the app particularly useful. The present study provides evidence that the Clinic Vitals mobile application can be a reliable substitute for in-person vital signs instruction. Recent educational advances have demonstrated that online videos, simulations, and mobile applications can be effective resources for nursing educators. There is potential for further study of the uses of educational mobile applications, including Clinic Vitals, for nursing education.