Accommodation in phakic and pseudophakic eyes measured with subjective and objective methods

PURPOSE To measure accommodation subjectively and objectively and assess anterior segment changes during accommodation in phakic eyes and pseudophakic eyes. SETTING Department of Ophthalmology, Medical Health and Science Centre, University of Debrecen, Debrecen, Hungary. DESIGN Case series. METHODS Subjective and objective accommodation measurements and pupillometry were performed in phakic and pseudophakic patients. Refraction and pupil diameter were recorded with different accommodation stimuli. Corneal higher-order aberrations (HOAs) and anterior chamber depths (ACDs) were detected with a rotating Scheimpflug camera. RESULTS The mean age of the 44 patients in the phakic group was 36.34 years ± 16.6 (SD) and of the 27 patients in the pseudophakic group, 69.3 ± 9.98 years. The mean subjective accommodation was 4.49 ± 3.48 diopters (D) in phakic eyes and showed significant correlation with age, spherical aberration, changes in pupil diameter, and ACD. The mean subjective accommodation was 0.50 ± 0.28 D in pseudophakic eyes. In phakic eyes, the mean objective accommodation was 0.46 ± 1.02 D, 1.06 ± 1.33 D, and 2.2 ± 1.9 D with 2.0 D, 3.0 D, and 5.0 D, respectively, of stimulus. In pseudophakic eyes, measurable objective accommodation was recorded. In phakic eyes, the correlations were significant between these values and age, changes in ACD, pupil size, and corneal spherical aberration. In pseudophakic eyes, the only correlation was with the spherical equivalent value. CONCLUSIONS The magnitude of accommodation was greater with subjective measures than objective measures. In pseudophakic eyes, senile miosis and HOAs can be regarded as underlying factors in subjective accommodation; however, objective accommodation is not clinically significant. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned

Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects

Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by treatment with the NAD+ booster nicotinamide mononucleotide (NMN) exerts significant vasoprotective effects, improving endothelium-dependent vasodilation, attenuating oxidative stress, and rescuing age-related changes in gene expression. Strong experimental evidence shows that dysregulation of microRNAs (miRNAs) has a role in vascular aging. The present study was designed to test the hypothesis that age-related NAD+ depletion is causally linked to dysregulation of vascular miRNA expression. A corollary hypothesis is that functional vascular rejuvenation in NMN-treated aged mice is also associated with restoration of a youthful vascular miRNA expression profile. To test these hypotheses, aged (24- month-old) mice were treated with NMN for 2 weeks and miRNA signatures in the aortas were compared to those in aortas obtained from untreated young and aged control mice. We found that protective effects of NMN treatment on vascular function are associated with anti-aging changes in the miRNA expression profile in the aged mouse aorta. The predicted regulatory effects of NMN-induced differentially expressed miRNAs in aged vessels include anti-atherogenic effects and epigenetic rejuvenation. Future studies will uncover the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments and determine the links between miRNAs regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging and major aging-related vascular diseases

Pharmacological or Genetic Depletion of Senescent Astrocytes Prevents Whole Brain Irradiation-Induced Impairment of Neurovascular Coupling Responses Protecting Cognitive Function in Mice

Whole brain irradiation (WBI, also known as whole brain radiation therapy or WBRT) is a mainstream therapy for patients with identifiable brain metastases and as a prophylaxis for microscopic malignancies. WBI accelerates brain aging, causing progressive cognitive dysfunction in ~ 50% of surviving patients, thus compromising quality of life. The mechanisms responsible for this WBI side effect remain obscure, and there are no effective treatments or prevention strategies. Here, we test the hypothesis that WBI induces astrocyte senescence, which contributes to impaired astrocytic neurovascular coupling (NVC) responses and the genesis of cognitive decline. To achieve this goal, we used transgenic p16-3MR mice, which allows the detection and selective elimination of senescent cells. We subjected these mice to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks). WBI-treated and control mice were tested for spatial memory performance (radial arm water maze), astrocyte-dependent NVC responses (whisker-stimulation-induced increases in cerebral blood flow, assessed by laser speckle contrast imaging), NVC-related gene expression, astrocytic release of eicosanoid gliotransmitters and the presence of senescent astrocytes (by flow cytometry, immunohistochemistry and gene expression profiling) at 6 months post-irradiation. WBI induced senescence in astrocytes, which associated with NVC dysfunction and impaired performance on cognitive tasks. To establish a causal relationship between WBI-induced senescence and NVC dysfunction, senescent cells were depleted from WBI-treated animals (at 3 months post-WBI) by genetic (ganciclovir treatment) or pharmacological (treatment with the BCL-2/BCL-xL inhibitor ABT263/Navitoclax, a known senolytic drug) means. In WBI-treated mice, both treatments effectively eliminated senescent astrocytes, rescued NVC responses, and improved cognitive performance. Our findings suggest that the use of senolytic drugs can be a promising strategy for preventing the cognitive impairment associated with WBI

Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans

Preclinical studies provide strong evidence that age-related impairment of neurovascular coupling (NVC) plays a causal role in the pathogenesis of vascular cognitive impairment (VCI). NVC is a critical homeostatic mechanism in the brain, responsible for adjustment of local cerebral blood flow to the energetic needs of the active neuronal tissue. Recent progress in geroscience has led to the identification of critical cellular and molecular mechanisms involved in neurovascular aging, identifying these pathways as targets for intervention. In order to translate the preclinical findings to humans, there is a need to assess NVC in geriatric patients as an endpoint in clinical studies. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that enables the investigation of local changes in cerebral blood flow, quantifying task-related changes in oxygenated and deoxygenated hemoglobin concentrations. In the present overview, the basic principles of fNIRS are introduced and the application of this technique to assess NVC in older adults with implications for the design of studies on the mechanistic underpinnings of VCI is discussed

Demonstration of Age-Related Blood-Brain Barrier Disruption and Cerebromicrovascular Rarefaction in Mice by Longitudinal Intravital Two-Photon Microscopy and Optical Coherence Tomography

Age-related blood-brain barrier (BBB) disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research, there is an urgent need for sensitive and easy-to-adapt imaging methods that enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice and that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that, in 24-mo-old C57BL/6J mice, cumulative permeability of the microvessels to fluorescent tracers of different molecular masses (0.3 to 40 kDa) is significantly increased compared with that of 5-mo-old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 wk) in vivo assessment of cerebromicrovascular health in preclinical geroscience research. New & Noteworthy: Methods are presented for longitudinal detection of age-related increase in blood-brain barrier permeability and microvascular rarefaction in the mouse cerebral cortex by intravital two-photon microscopy and optical coherence tomography