The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD.

Purpose To investigate the changes of the retinal microvascular network and microcirculation in high myopia. Design A cross-sectional, matched, comparative clinical study. Participants Twenty eyes of twenty subjects with non-pathological high myopia (28 ± 5 Years) with a refractive error of −6.31 ± 1.23 Diopters (mean ± standard deviation) and twenty eyes of twenty age- and gender-matched control subjects (30 ± 6 years) with a refractive error of −1.40 ± 1.00 Diopters were recruited. Methods Optical coherence tomography angiography (OCTA) was used to image the retinal microvascular network, which was later quantified by fractal analysis (box counting, Dbox, representing vessel density) in both superficial and deep vascular plexuses. The retinal function imager (RFI) was used to image the retinal microvessel blood flow velocity (BFV). The BFV and microvascular density in the myopia group were corrected for ocular magnification using Bennett’s formula. Results The density of both superficial and deep microvascular plexuses was significantly decreased in the myopia group in comparison to the controls (P < 0.05). The decrease of the microvessel density of the annular zone (0.6 – 2.5 mm), measured as Dbox, was 2.1% and 2.9% in superficial and deep vascular plexuses, respectively. The microvessel density reached a plateau from 0.5 mm to 1.25 mm from the fovea in both groups, but that in myopic group was about 3% lower than the control group. No significant differences were detected between the groups in retinal microvascular BFV in either arterioles or venules (P > 0.05). Microvascular densities in both superficial (r = −0.45, P = 0.047) and deep (r = −0.54, P = 0.01) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. No correlations were observed between BFV and vessel density (P > 0.05). Conclusions Retinal microvascular decrease was observed in the high myopia subjects, whereas the retinal microvessel BFV remained unchanged. The retinal microvascular network alteration may be attributed to ocular elongation that occurs with the progression of myopia. The novel quantitative analyses of the retinal microvasculature may help to characterize the underlying pathophysiology of myopia and enable early detection and prevention of myopic retinopathy.

PurposeTo characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects.MethodsSeventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI).ResultsCompared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05).ConclusionsDuring aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components.

Purpose To develop, test and validate functional slit lamp biomicroscopy (FSLB) for generating non-invasive bulbar conjunctival microvascular perfusion maps (nMPMs) and assessing morphometry and hemodyanmics. Methods FSLB was adapted from a traditional slit-lamp microscope by attaching a digital camera to image the bulbar conjunctiva to create nMPMs and measure venular blood flow hemodyanmics. High definition images with a large field of view were obtained on the temporal bulbar conjunctiva for creating nMPMs. A high imaging rate of 60 frame per second and a ~210× high magnification were achieved using the camera inherited high speed setting and movie crop function, for imaging hemodyanmics. Custom software was developed to segment bulbar conjunctival nMPMs for further fractal analysis and quantitatively measure blood vessel diameter, blood flow velocity and flow rate. Six human subjects were imaged before and after 6 hours of wearing contact lenses. Monofractal and multifractal analyses were performed to quantify fractality of the nMPMs. Results The mean bulbar conjunctival vessel diameter was 18.8 ± 2.7 μm at baseline and increased to 19.6 ± 2.4 μm after 6 hours of lens wear (P = 0.020). The blood flow velocity was increased from 0.60 ± 0.12 mm/s to 0.88 ± 0.21 mm/s (P = 0.001). The blood flow rate was also increased from 129.8 ± 59.9 pl/s to 207.2 ± 81.3 pl/s (P = 0.001). Bulbar conjunctival nMPMs showed the intricate details of the bulbar conjunctival microvascular network. At baseline, fractal dimension was 1.63 ± 0.05 and 1.71 ± 0.03 analyzed by monofractal and multifractal analysis, respectively. Significant increases in fractal dimensions were found after 6 hours of lens wear (P < 0.05). Conclusions Microvascular network’s fractality, morphometry and hemodyanmics of the human bulbar conjunctiva can be measured easily and reliably using FSLB. The alternations of the fractal dimensions, morphometry and hemodyanmics during contact lens wear may indicate ocular microvascular responses to contact lens wear.

PURPOSE. To investigate the retinal vascular network alterations in highly myopic eyes.METHODS. Thirty-three highly myopic eyes from 21 subjects and 47 mildly myopic or emmetropic eyes from 24 healthy control subjects were enrolled. Optical coherence tomography angiography (OCTA) was used to image the superficial, deep, and whole retinal vascular plexuses at the macular region. Highly myopic eye images were analyzed after adjusting the ocular magnification using Bennett's formula. Fractal analysis (box counting method, D box ) representing vessel density was performed in different annular and quadrantile zones of both large vessels and microvessels. Correlations between the vascular density, axial length, and spherical equivalent refractive error were analyzed. RESULTS.The average density (D box ) of the superficial retinal annular zone (0.6-2.5 mm) microvessels was 1.741 6 0.018 in highly myopic eyes and was shown to be significantly lower than that of the controls (1.773 6 0.010, P < 0.001). Individual annular zone (bandwidth of 0.16 mm) analysis of highly myopic eyes revealed a significant level of microvessel alteration in all zones compared with the same zones in control eyes (P < 0.001). Furthermore, in the highly myopic group, the microvessel density was significantly correlated with axial length elongation in all three layers (r ¼ À0.38 to À0.48; P < 0.05).CONCLUSIONS. This study reveals retinal microvascular network alterations in highly myopic eyes, which correlates with axial length elongation. Fractal analysis of the microvasculature by OCTA images may help to characterize the underlying pathophysiological mechanisms involved in high myopia.

Objective: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. Methods: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High-and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis.View this article online at wileyonlinelibrary.com.

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