Risk of visual impairment according to the comorbidity of systemic and ocular diseases.

PURPOSE: To investigate the risk of visual impairment (VI) based on the presence or absence of four diseases: hypertension (HTN), diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). METHODS: This retrospective population-based study included 1,000,000 randomly selected participants from the National Health Checkup Program database between 2015 and 2016. VI was defined as a presenting visual acuity ≤ 0.5 in the better eye. The participants were divided into 12 groups according to the presence or absence of disease. Adjusting for age and sex, the risk of VI in each disease group was analyzed and compared with the others. RESULTS: Among the 1,000,000 participants, 88,931 (8.89%) had VI. The odds ratios (ORs) of age, male sex, HTN, DM, glaucoma, and DR for VI were 1.06 (95% CI, 1.05-1.06), 0.52 (95% CI, 0.52-0.53), 1.11 (95% CI, 1.09-1.13), 1.07 (95% CI, 1.05-1.09), 0.92 (95% CI, 0.90-0.74), and 1.29 (95% CI, 1.25-1.34), respectively (all P < 0.001). The group with HTN, DM, glaucoma, and DR had the highest OR of 1.98 (P < 0.001) compared to the healthy group. HTN, DM, and DR were positively correlated with VI in all groups. Glaucoma was positively correlated in the group with DM and DR and in the group with HTN, DM, and DR (ORs 1.18, 1.11, all P < 0.05); however, it demonstrated a negative correlation in the other groups (ORs 0.85-0.93, all P < 0.05). CONCLUSION: HTN, DM, and DR, either alone or in combination, increase the risk of VI. Glaucoma also increases the risk when combined with DR; however, it has a negative correlation with VI in the absence of DR. Periodic ophthalmologic examinations for glaucoma, which primarily affects the peripheral visual field and not central visual acuity, might help prevent VI caused by other diseases.

Age-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months.

Purpose: This study provides a systematic evaluation of age-related changes in RPE cell structure and function using a morphometric approach. We aim to better capture nuanced predictive changes in cell heterogeneity that reflect loss of RPE integrity during normal aging. Using C57BL6/J mice ranging from P60-P730, we sought to evaluate how regional changes in RPE shape reflect incremental losses in RPE cell function with advancing age. We hypothesize that tracking global morphological changes in RPE is predictive of functional defects over time. Methods: We tested three groups of C57BL/6J mice (young: P60-180; Middle-aged: P365-729; aged: 730+) for function and structural defects using electroretinograms, immunofluorescence, and phagocytosis assays. Results: The largest changes in RPE morphology were evident between the young and aged groups, while the middle-aged group exhibited smaller but notable region-specific differences. We observed a 1.9-fold increase in cytoplasmic alpha-catenin expression specifically in the central-medial region of the eye between the young and aged group. There was an 8-fold increase in subretinal, IBA-1-positive immune cell recruitment and a significant decrease in visual function in aged mice compared to young mice. Functional defects in the RPE corroborated by changes in RPE phagocytotic capacity. Conclusions: The marked increase of cytoplasmic alpha-catenin expression and subretinal immune cell deposition, and decreased visual output coincide with regional changes in RPE cell morphometrics when stratified by age. These cumulative changes in the RPE morphology showed predictive regional patterns of stress associated with loss of RPE integrity.

Failure to mate enhances investment in behaviors that may promote mating reward and impairs the ability to cope with stressors via a subpopulation of Neuropeptide F receptor neurons.

Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associated with obtaining these rewards is mediated by stress-response pathways, the activation of which can impair health and shorten lifespan. While much research has been devoted to understanding mechanisms underlying the way by which natural rewards are processed by the reward system, less attention has been given to the consequences of failure to obtain a desirable reward. As a model system to study the impact of failure to obtain a natural reward, we used the well-established courtship suppression paradigm in Drosophila melanogaster as means to induce repeated failures to obtain sexual reward in male flies. We discovered that beyond the known reduction in courtship actions caused by interaction with non-receptive females, repeated failures to mate induce a stress response characterized by persistent motivation to obtain the sexual reward, reduced male-male social interaction, and enhanced aggression. This frustrative-like state caused by the conflict between high motivation to obtain sexual reward and the inability to fulfill their mating drive impairs the capacity of rejected males to tolerate stressors such as starvation and oxidative stress. We further show that sensitivity to starvation and enhanced social arousal is mediated by the disinhibition of a small population of neurons that express receptors for the fly homologue of neuropeptide Y. Our findings demonstrate for the first time the existence of social stress in flies and offers a framework to study mechanisms underlying the crosstalk between reward, stress, and reproduction in a simple nervous system that is highly amenable to genetic manipulation.

Comparison of quantification of intraretinal hard exudates between optical coherence tomography en face image versus fundus photography.

PURPOSE: To compare the quantification of intraretinal hard exudate (HE) using en face optical coherence tomography (OCT) and fundus photography. METHODS: Consecutive en face images and corresponding fundus photographs from 13 eyes of 10 patients with macular edema associated with diabetic retinopathy or Coats' disease were analyzed using the machine-learning-based image analysis tool, "ilastik." RESULTS: The overall measured HE area was greater with en face images than with fundus photos (en face: 0.49 ± 0.35 mm2 vs. fundus photo: 0.34 ± 0.34 mm2, P < 0.001). However, there was an excellent correlation between the two measurements (intraclass correlation coefficient [ICC] = 0.844). There was a negative correlation between HE area and central macular thickness (CMT) (r = -0.292, P = 0.001). However, HE area showed a positive correlation with CMT in the previous several months, especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy (CMT 3 months before: r = 0.349, P = 0.001; CMT 4 months before: r = 0.287, P = 0.012). CONCLUSION: Intraretinal HE can be reliably quantified from either en face OCT images or fundus photography with the aid of an interactive machine learning-based image analysis tool. HE area changes lagged several months behind CMT changes, especially in eyes treated with anti-VEGF injections.

Factors affecting optical coherence tomography angiography signal strength index in patients receiving intravitreal injection treatment.

PURPOSE: To investigate the clinical factors affecting optical coherence tomography angiography (OCTA) signal strength index (SSI) and its change after intravitreal injection treatment in patients with retinal disorders. METHODS: OCTA data from 186 eyes of 166 patients with various retinal disorders including age-related macular degeneration, diabetic macular edema (DME), and retinal vein occlusions who received intravitreal injections were analyzed. The associations between SSI and clinical factors, including age, best-corrected visual acuity (BCVA), media opacity severity, and central macular thickness (CMT), were evaluated both before and after injection. RESULTS: After injection, BCVA improved and CMT decreased significantly, and SSI increased significantly (p = 0.030). BCVA showed a significant positive correlation with media opacity severity before and after injection and with CMT only before injection. In the multivariate analysis, age, presence of DME, BCVA, and media opacity severity were negatively associated with SSI both before and after injection, while CMT was negatively associated with SSI only before injection. After injection, a negative correlation was found between SSI change and both BCVA and CMT change. CONCLUSION: Our findings suggest that OCTA SSI is influenced by various clinical factors, including age, visual acuity, media opacity severity, and macular thickening, especially in cases of DME. The results also indicate that SSI may decrease in patients with macular disorders due to the presence of macular edema and the associated decrease in visual acuity. Therefore, it is crucial to consider these factors when interpreting OCTA data and ensure an adequate level of SSI.

Tractional Retinal Detachment in Eyes with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy and Posterior Vitreous Detachment in Fellow Eye.

PURPOSE: To predict the presence of tractional retinal detachment (TRD) in eyes with dense vitreous hemorrhage (VH) and proliferative diabetic retinopathy (PDR) by evaluating the status of posterior vitreous detachment (PVD) in fellow eyes using optical coherence tomography (OCT). METHODS: A total of 44 eyes from 22 patients who underwent vitrectomy due to dense VH with PDR were enrolled. Using OCT, the PVD status in the fellow eye was divided into two groups (incomplete and complete PVD). The incomplete PVD group included eyes without PVD and eyes with partial PVD. B-scan ultrasonography was performed on eyes with dense VH to evaluate the presence of TRD. Both OCT and B-scan images were reviewed by four ophthalmologists (two novices and two experienced), and the interobserver agreement was evaluated. RESULTS: There was a difference in the interobserver agreement regarding the presence of TRD in eyes with dense VH evaluated by B scan between novice and experienced ophthalmologists (novice, κ = 0.421 vs. experienced, κ = 0.814), although there was no difference between novice and experienced ophthalmologists in the interobserver agreement regarding the status of PVD in the fellow eye evaluated by OCT (novice, κ = 1.000 vs. experienced, κ = 1.000). All observed TRD during vitrectomy occurred in eyes with incomplete PVD in the fellow eye. Logistic regression analysis revealed a statistically significant relation between TRD and the age of the patient (odds ratio [OR], 0.874; p = 0.047), and between TRD and incomplete PVD in the fellow eye evaluated by OCT (OR, 13.904; p = 0.042). CONCLUSIONS: Evaluation of the PVD status in the fellow eye using OCT may be a useful predictor for detecting the presence of TRD in eyes with dense VH and PDR.

Approval status and characteristics of work-related musculoskeletal disorders among Korean workers in 2020.

Background: This study aimed to investigate the characteristics of work-related musculoskeletal disorders (WRMSDs) in occupational disease claims and identify patterns of WRMSDs for each body part by industry and occupation. Methods: This study analyzed the raw data of occupational disease claims for musculoskeletal disorders deliberated by the Occupational Disease Decision Committee of the Korea Workers' Compensation & Welfare Service in 2020. The data was classified into 6 body parts with the highest numbers of occupational disease cases by using the complete enumeration data on principal diagnoses and 4 types of subdiagnoses in the raw data. The characteristics and approval rates of WRMSDs by body part, industry and occupation were examined and summarized. Results: A total of 13,015 occupational disease cases for WRMSDs were classified, and lumbar spinal (back) diseases accounted for the largest proportion of claimed diseases, followed by shoulder, elbow, wrist, knee, and neck diseases in a descending order. The occupations with the highest and second highest numbers of occupational disease cases by body part were found to be automobile assemblers and production-related elementary workers for the neck, school meal service workers and cooks for the back, construction frame mold carpenters and school meal service workers for the shoulder, elementary workers in mining and food service workers for the elbow, food service workers and automobile parts assemblers for the wrist, and ship welders and school meal service workers for the knee. Conclusions: This study examined the characteristics and approval status of WRMSDs by body part and occupation. Based on the study results, management strategies for the prevention of WRMSDs should be established regarding occupations with a high risk of WRMSDs for each body part.

Standards for recognition and approval rate of occupational cerebro-cardiovascular diseases in Korea.

Background: Although working hours have decreased in Korea, they are still high compared to that of other countries. In Korea, cardiovascular and cerebrovascular diseases (CCVDs) related to overwork in Korea continually occur, and the social burden from overwork is estimated to be high. This study investigated the amendment of regulations affecting the approval rate of occupational CCVDs. Methods: The change in approval rate of occupational CCVDs and related regulations were investigated using the Act and public notice on the standards for recognition of occupational CCVDs and the yearbooks of the Ministry of Employment and Labor. The CCVD mortality was estimated using data on the number of deaths according to the cause of death, the number of employed people, and resident registration population aged 15-64 years. The cumulative mortality of CCVDs was estimated using the Kaplan-Meier method. Results: Since the establishment of the standards for recognition in Korea in 1982, the scope of occupational diseases has been expanded to include intracerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, myocardial infarction, and aortic dissection. In 2013, the concept of working hours was introduced in chronic overwork. The approval rate of occupational CCVDs was 44.7% in 2006, which decreased to 12.9% in 2011. After the improvement of related regulations, the approval rate increased to 41.3% in 2018. From 2000 to 2017, the CCVD mortality of both the unemployed and employed tended to decrease, and their cumulative CCVD mortalities were 549.3 and 319.7 per 100,000 people, respectively. Conclusions: CCVDs are recognized as occupational diseases in Korea. The amendments to the standards for recognition, the introduction of the Occupational Disease Adjudication Committee, the principle of presumption, and the reduction of working hours have changed the approval rate of occupational CCVDs. A strategic approach is needed to further reduce the incidence of CCVDs.

Comparative analysis on intaglio surface trueness, wear volume loss of antagonist, and fracture resistance of full-contour monolithic zirconia crown for single-visit dentistry under simulated mastication.

PURPOSE: This analysis aimed to evaluate the intaglio surface trueness, antagonist's wear volume loss, and fracture resistance of full-contour crowns of (Y, Nb)-stabilized fully-sintered zirconia (FSZ), 4 mol% or 5 mol% yttria-stabilized partially sintered zirconia (4YZ or 5YZ) with high-speed sintering. MATERIALS AND METHODS: A total of 42 zirconia crowns were separated into three groups: FSZ, 4YZ, and 5YZ (n = 14). The intaglio surface trueness of the crowns was evaluated at the inner surface, occlusal, margin, and axial areas and reported as root-mean-square, positive and negative average deviation. Half of the specimens were aged for 120,000 cycles in the chewing simulator, and the wear volume loss of antagonist was measured. Before and after chewing, the fracture load was measured for each group. The trueness values were analyzed with Welch's ANOVA, and the wear volume loss with the Kruskal-Wallis tests. Effect of the zirconia type and aging on fracture resistance of crowns was tested using two-way ANOVA. RESULTS: The intaglio surface trueness measured at four different areas of the crown was less than 50 µm, regardless of the type of zirconia. No significant P in wear volume loss of antagonists were detected among the groups (P > .05). Both the type of zirconia and aging showed statistically significant effects on fracture resistance (P < .05). CONCLUSION: The full-contour crowns of FSZ as well as 4YZ or 5YZ with high-speed sintering were clinically acceptable, in terms of intaglio surface trueness, antagonist's wear volume loss, and fracture resistance after simulated mastication.

Evaluation of intaglio surface trueness, wear, and fracture resistance of zirconia crown under simulated mastication: a comparative analysis between subtractive and additive manufacturing.

PURPOSE: This in-vitro analysis aimed to compare the intaglio trueness, the antagonist's wear volume loss, and fracture load of various single-unit zirconia prostheses fabricated by different manufacturing techniques. MATERIALS AND METHODS: Zirconia crowns were prepared into four different groups (n = 14 per group) according to the manufacturing techniques and generations of the materials. The intaglio surface trueness (root-mean-square estimates, RMS) of the crown was measured at the marginal, axial, occlusal, and inner surface areas. Half of the specimens were artificially aged in the chewing simulator with 120,000 cycles, and the antagonist's volume loss after aging was calculated. The fracture load for each crown group was measured before and after hydrothermal aging. The intaglio trueness was evaluated with Welch's ANOVA and the antagonist's volume loss was assessed by the Kruskal-Wallis tests. The effects of manufacturing and aging on the fracture resistance of the tested zirconia crowns were determined by two-way ANOVA. RESULTS: The trueness analysis of the crown intaglio surfaces showed surface deviation (RMS) within 50 µm, regardless of the manufacturing methods (P = .053). After simulated mastication, no significant differences in the volume loss of the antagonists were observed among the zirconia groups (P = .946). The manufacturing methods and simulated chewing had statistically significant effects on the fracture resistance (P < .001). CONCLUSION: The intaglio surface trueness, fracture resistance, and antagonist's wear volume of the additively manufactured 3Y-TZP crown were clinically acceptable, as compared with those of the 4Y- or 5Y-PSZ crowns produced by subtractive milling.

Vogt-Koyanagi-Harada Disease following mRNA-1273 (Moderna) COVID-19 Vaccination.

PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease following mRNA-1273 (Moderna) COVID-19 vaccination. METHODS: Retrospective case report. RESULTS: A 50-year-old Korean woman developed bilateral serous retinal detachment 35 days after the first dose of COVID-19 mRNA vaccination (mRNA-1273, Moderna). She experienced adverse effects such as erythema and pain at the injection site, headache, myalgia, and allergy symptoms prior to ocular manifestation. She was diagnosed with Vogt-Koyanagi-Harada (VKH) disease. After treatment with oral prednisolone, the serous retinal detachment resolved and vision improved. CONCLUSION: COVID-19 vaccination might be associated with VKH disease development, and the ingredients of the mRNA vaccine or viral peptide encoded by mRNA may have activated the immunological process and induced VKH disease.

Choroidal vascularity index of patients with coronary artery disease.

We investigated the changes in subfoveal choroidal thickness and choroidal vascularity index (CVI) and their relationship with the severity of coronary artery stenosis in patients with cardiovascular risk factors and symptoms suggestive of coronary artery disease (CAD). Ninety patients who underwent coronary angiography (CAG) for evaluation of their coronary artery status and cardiac symptoms were included. Forty-two patients showed no evidence of CAD; 31 patients had one to two vessel disease; and 17 had a triple vessel disease. There were no significant differences in the subfoveal choroidal thickness among the three groups; however, the CVI in the triple vessel disease group was lower than those in the other groups. The CVI values were good predictors of the presence of triple-vessel disease (p = 0.020). Multivariate logistic regression analysis results revealed that male sex (odds ratio 5.4, p = 0.049), hypertension (odds ratio 4.9, p = 0.017), and CVI (%, odds ratio 0.8, p = 0.016) were significant factors associated with the presence of triple vessel disease. Although CVI may not be a sensitive marker for detecting early changes in the coronary artery, it may be helpful in indicating severe CAD.

AICAR upregulates ABCA1/ABCG1 expression in the retinal pigment epithelium and reduces Bruch's membrane lipid deposit in ApoE deficient mice.

The etiology of age-related macular degeneration (AMD) is diverse; however, recent evidence suggests that the lipid metabolism-cholesterol pathway might be associated with the pathophysiology of AMD. The ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1, are essential for the formation of high-density lipoprotein (HDL) and the regulation of macrophage cholesterol efflux. The failure of retinal or retinal pigment epithelium (RPE) cholesterol efflux to remove excess intracellular lipids causes morphological and functional damage to the retina. In this study, we investigated whether treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMP-activated protein kinase (AMPK) activator, improves RPE cholesterol efflux and Bruch's membrane (BM) lipid deposits. The protein and mRNA levels of ABCA1 and ABCG1 in ARPE-19 cells and retinal and RPE/choroid tissue from apolipoprotein E-deficient (ApoE-/-) mice were evaluated after 24 weeks of AICAR treatment. The cholesterol efflux capacity of ARPE-19 cells and the cholesterol-accepting capacity of apoB-depleted serum from mice were measured. The thickness of the BM and the degree of lipid deposition were evaluated using electron microscopy. AICAR treatment increased the phosphorylation of AMPK and the protein and mRNA expression of ABCA1 and ABCG1 in vitro. It promoted cholesterol efflux from ARPE-19 cells and upregulated the protein and mRNA levels of ABCA1 and ABCG1 in the retina and RPE in vivo. ApoB-depleted serum from the AICAR-treated group showed enhanced cholesterol-accepting capacity. Long-term treatment with AICAR reduced BM thickening and lipid deposition in ApoE-/- mice. In conclusion, AICAR treatment increased the expression of lipid transporters in the retina and RPE in vivo, facilitated intracellular cholesterol efflux from the RPE in vitro, and improved the functionality of HDL to accept cholesterol effluxed from the cell, possibly via AMPK activation. Collectively, these effects might contribute to the improvement of early age-related pathologic changes in the BM. Pharmacological improvement of RPE cholesterol efflux via AMPK activation may be a potential treatment strategy for AMD.

Bioaccumulation of therapeutic drugs by human gut bacteria.

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.

Adaptive laboratory evolution of microbial co-cultures for improved metabolite secretion.

Adaptive laboratory evolution has proven highly effective for obtaining microorganisms with enhanced capabilities. Yet, this method is inherently restricted to the traits that are positively linked to cell fitness, such as nutrient utilization. Here, we introduce coevolution of obligatory mutualistic communities for improving secretion of fitness-costly metabolites through natural selection. In this strategy, metabolic cross-feeding connects secretion of the target metabolite, despite its cost to the secretor, to the survival and proliferation of the entire community. We thus co-evolved wild-type lactic acid bacteria and engineered auxotrophic Saccharomyces cerevisiae in a synthetic growth medium leading to bacterial isolates with enhanced secretion of two B-group vitamins, viz., riboflavin and folate. The increased production was specific to the targeted vitamin, and evident also in milk, a more complex nutrient environment that naturally contains vitamins. Genomic, proteomic and metabolomic analyses of the evolved lactic acid bacteria, in combination with flux balance analysis, showed altered metabolic regulation towards increased supply of the vitamin precursors. Together, our findings demonstrate how microbial metabolism adapts to mutualistic lifestyle through enhanced metabolite exchange.

Electrophysiologic and Morphologic Strain Differences in a Low-Dose NaIO3-Induced Retinal Pigment Epithelium Damage Model.

Purpose: We aimed to explore differences in the NaIO3-elicited responses of retinal pigment epithelium (RPE) and other retinal cells associated with mouse strains and dosing regimens. Methods: One dose of NaIO3 at 10 or 15 mg/kg was given intravenously to adult male C57BL/6J and 129/SV-E mice. Control animals were injected with PBS. Morphologic and functional changes were characterized by spectral domain optical coherence tomography, electroretinography, histologic, and immunofluorescence techniques. Results: Injection with 10 mg/kg of NaIO3 did not cause consistent RPE or retinal changes in either strain. Administration of 15 mg/kg of NaIO3 initially induced a large transient increase in scotopic electroretinography a-, b-, and c-wave amplitudes within 12 hours of injection, followed by progressive structural and functional degradation at 3 days after injection in C57BL/6J mice and at 1 week after injection in 129/SV-E mice. RPE cell loss occurred in a large posterior-central lesion with a ring-like transition zone of abnormally shaped cells starting 12 hours after NaIO3 treatment. Conclusions: NaIO3 effects depended on the timing, dosage, and mouse strain. The RPE in the periphery was spared from damage compared with the central RPE. The large transient increase in the electroretinography was remarkable. Translational Relevance: This study is a phase T1 translational research study focusing on the development and validation of a mouse model of RPE damage. It provides a detailed foundation for future research, informing choices of mouse strain, dosage, and time points to establish NaIO3-induced RPE damage.

Genome editing of hPSCs: Recent progress in hPSC-based disease modeling for understanding disease mechanisms.

Generation of proper models for studying human genetic diseases has been hindered until recently by the scarcity of primary cell samples from genetic disease patients and inefficient genetic modification tools. However, recent advances in clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and human induced pluripotent stem cells (hiPSCs) have provided an opportunity to explore the function of pathogenic variants and obtain gene-corrected cells for autologous cell therapy. In this chapter, we address recent applications of CRISPR/Cas9 to hiPSCs in genetic diseases, including neurodegenerative, cardiovascular, and rare diseases.

Age-Related Retinal Changes in Wild-Type C57BL/6J Mice Between 2 and 32 Months.

Purpose: The purpose of this study was to extend our understanding of how aging affects normal retina function and morphology in wild-type C57BL/6J mice, by analyzing electrophysiological recordings and in vivo and post mortem anatomy. Methods: Electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT), and confocal scanning laser ophthalmoscope (cSLO) in vivo images were obtained from mice between the ages of 2 and 32 months in four groups: group 1 (<0.5 years), group 2 (1.0-1.5 years), group 3 (1.5-2.0 years), and group 4 (>2.0 years). Afterward, mouse bodies and eyes were weighed. Eyes were stained with hematoxylin and eosin (H&E) and cell nuclei were quantified. Results: With aging, mice showed a significant reduction in both a- and b-wave ERG amplitudes in scotopic and photopic conditions. Additionally, total retina and outer nuclear layer (ONL) thickness, as measured by SD-OCT images, were significantly reduced in older groups. The cSLO images showed an increase in auto-fluorescence at the photoreceptor-RPE interface as age increases. H&E cell nuclei quantification showed significant reduction in the ONL in older ages, but no differences in the inner nuclear layer (INL) or ganglion cell layer (GCL). Conclusions: By using multiple age groups and extending the upper age limit of our animals to approximately 2.65 years (P970), we found that natural aging causes negative effects on retinal function and morphology in a gradual, rather than abrupt, process. Future studies should investigate the exact mechanisms that contribute to these gradual declines in order to discover pathways that could potentially serve as therapeutic targets.

Draft Genome Sequences of Five Fungal Strains Isolated from Kefir.

We present the annotated draft genome sequences of five fungal strains isolated from kefir grains. These isolates included three ascomycetous (Candida californica, Kazachstania exigua, and Kazachstania unispora) and one basidiomycetous (Rhodotorula mucilaginosa) species. The results revealed a detailed overview of the metabolic features of kefir fungi that will be potentially useful in biotechnological applications.

Computational Model-Based Estimation of Mouse Eyeball Structure From Two-Dimensional Flatmount Microscopy Images.

Purpose: Retinal pigment epithelial (RPE) cells serve as a supporter for the metabolism and visual function of photoreceptors and a barrier for photoreceptor protection. Morphology dynamics, spatial organization, distribution density, and growth patterns of RPE cells are important for further research on these RPE main functions. To enable such investigations within the authentic eyeball structure, a new method for estimating the three-dimensional (3D) eyeball sphere from two-dimensional tissue flatmount microscopy images was investigated. Methods: An error-correction term was formulated to compensate for the reconstruction error as a result of tissue distortions. The effect of the tissue-distortion error was evaluated by excluding partial data points from the low- and high-latitude zones. The error-correction parameter was learned automatically using a set of samples with the ground truth eyeball diameters measured with noncontact light-emitting diode micrometry at submicron accuracy and precision. Results: The analysis showed that the error-correction term in the reconstruction model is a valid method for modeling tissue distortions in the tissue flatmount preparation steps. With the error-correction model, the average relative error of the estimated eyeball diameter was reduced from 14% to 5%, and the absolute error was reduced from 0.22 to 0.03 mm. Conclusions: A new method for enabling RPE morphometry analysis with respect to locations on an eyeball sphere was created, an important step in increasing RPE research and eye disease diagnosis. Translational Relevance: This method enables one to derive RPE cell information from the 3D eyeball surface and helps characterize eyeball volume growth patterns under diseased conditions.