Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction.

Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term nicotinamide treatment as a neuroprotective therapy for human glaucoma.

INCREASED FOVEAL GANGLION CELL AND INNER PLEXIFORM LAYER THICKNESS IN CHILDREN AGED 6.5 YEARS BORN EXTREMELY PRETERM.

PURPOSE: To analyze the ganglion cell layer and inner plexiform layer (GCL+) thickness in children born extremely preterm and control children. METHODS: A study of 6.5-year-old children born before the gestational age of 27 weeks and age-matched controls. The GCL+ thickness and foveal depth (FD) were analyzed in a single optical coherence tomography B-scan. Association with neonatal risk factors and sex was investigated. Extremely preterm was divided into no, mild, and severe retinopathy of prematurity, retinopathy of prematurity treatment, and no, mild, and severe intraventricular hemorrhage. RESULTS: Adequate measurements were obtained from 89 children born extremely preterm and 92 controls. Extremely preterm children had increased total (5 µm, P < 0.001) and central (21 µm, P < 0.001) GCL+ thickness and reduced FD (-53 µm, P < 0.001) compared with controls. Extremely preterm children receiving retinopathy of prematurity treatment had increased GCL+ thickness and reduced FD compared with other subgroups. Sex and gestational age were associated with increased central GCL+ thickness and reduced FD. Reduced total GCL+ thickness was associated with severe intraventricular hemorrhage. CONCLUSION: Extremely preterm birth can cause incomplete extrusion of the GCL+ and reduced FD. Retinopathy of prematurity treatment, gestational age, and male sex were associated to increased central GCL+ thickness and reduced FD, while severe intraventricular hemorrhage was associated with reduced total GCL+ thickness.