Photostasis and photosynthetic adaptation to polar life.

Photostasis is the light-dependent maintenance of energy balance associated with cellular homeostasis in photoautotrophs. We review evidence that illustrates how photosynthetic adaptation in polar photoautrophs such as aquatic green algae, cyanobacteria, boreal conifers as well as terrestrial angiosperms exhibit an astonishing plasticity in structure and function of the photosynthetic apparatus. This plasticity contributes to the maintenance of photostasis, which is essential for the long-term survival in the seemingly inhospitable Antarctic and Arctic habitats. However, evidence indicates that polar photoautrophic species exhibit different functional solutions for the maintenance of photostasis. We suggest that this reflects, in part, the genetic diversity symbolized by inherent genetic redundancy characteristic of polar photoautotrophs which enhances their survival in a thermodynamically challenging environment.

Effects of Voice Pitch on Social Perceptions Vary With Relational Mobility and Homicide Rate.

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.

Social mindfulness and prosociality vary across the globe.

Humans are social animals, but not everyone will be mindful of others to the same extent. Individual differences have been found, but would social mindfulness also be shaped by one's location in the world? Expecting cross-national differences to exist, we examined if and how social mindfulness differs across countries. At little to no material cost, social mindfulness typically entails small acts of attention or kindness. Even though fairly common, such low-cost cooperation has received little empirical attention. Measuring social mindfulness across 31 samples from industrialized countries and regions (n = 8,354), we found considerable variation. Among selected country-level variables, greater social mindfulness was most strongly associated with countries' better general performance on environmental protection. Together, our findings contribute to the literature on prosociality by targeting the kind of everyday cooperation that is more focused on communicating benevolence than on providing material benefits.

Socio-economic and ethnic disparities in childhood cancer survival, Yorkshire, UK.

BACKGROUND: Establishing the existence of health inequalities remains a high research and policy agenda item in the United Kingdom. We describe ethnic and socio-economic differences in paediatric cancer survival, focusing specifically on the extent to which disparities have changed over a 20-year period. METHODS: Cancer registration data for 2674 children (0-14 years) in Yorkshire were analysed. Five-year survival estimates by ethnic group (south Asian/non-south Asian) and Townsend deprivation fifths (I-V) were compared over time (1997-2016) for leukaemia, lymphoma, central nervous system (CNS) and other solid tumours. Hazard ratios (HR: 95% CI) from adjusted Cox models quantified the joint effect of ethnicity and deprivation on mortality risk over time, framed through causal interpretation of the deprivation coefficient. RESULTS: Increasing deprivation was associated with significantly higher risk of death for children with leukaemia (1.11 (1.03-1.20)) and all cancers between 1997 and 2001. While we observed a trend towards reducing differences in survival over time in this group, a contrasting trend was observed for CNS tumours whereby sizeable variation in outcome remained for cases diagnosed until 2012. South Asian children with lymphoma had a 15% reduced chance of surviving at least 5 years compared to non-south Asian, across the study period. DISCUSSION: Even in the United Kingdom, with a universally accessible healthcare system, socio-economic and ethnic disparities in childhood cancer survival exist. Findings should inform where resources should be directed to provide all children with an equitable survival outcome following a cancer diagnosis.

The Role of Humor Production and Perception in the Daily Life of Couples: An Interest-Indicator Perspective.

In established relationships, are couples who are funny more satisfied with each other, or are satisfied couples more able to see the funny side of their partners? Much research has examined the evolutionary function of humor in relationship initiation, but not in relationship maintenance. Using a dyadic daily-diary study composed of college students from Singapore, results showed that relationship quality was positively associated with same-day humor production and perception. Importantly, and consistent with an interest-indicator perspective in which humor exchanges communicate relationship interest, relationship quality was also positively associated with next-day humor production and perception, and across both sexes. Results also indicated some support for a sexual-selection perspective in which humor exchanges predicted only same- and next-day satisfaction, but not commitment. Our findings suggest that humor can ultimately function as a strategy to monitor and maintain established relationships.

The accumulated oxygen deficit as an indicator of the ischemic retinal insult.

We here attempt to improve quantification of the ischemic retinal insult, that is, what is imposed on the retinal tissue by ischemia, especially in experimental models of ischemia. The ischemic retinal insult initiates the ischemic retinal injury (or outcome). Accordingly, it is reasonable to assume that the better the quantification of the insult, the better the correlation with, and thereby estimation of, the injury. The insult seldom has been quantified in terms of the relevant physiological factors, especially in connection with the rate of oxygen delivery (DO2). We here propose the accumulated oxygen deficit (AO2D) as an indicator of the ischemic retinal insult. We hypothesized that AO2D is correlated with the rate of oxygen metabolism measured 1 h after reperfusion following an episode of ischemia (MO2_1_Hr). Previously, we showed that MO2_1_Hr is related to the electroretinogram amplitude and the retinal thickness when they are measured seven days after reperfusion. We studied 27 rats, as well as 26 rats from our published data on retinal ischemia in which we had measurements of DO2 and duration of ischemia (T) of various levels and durations. We also measured DO2 in 29 rats treated with sham surgery. Ischemia was induced by either ipsilateral or bilateral common carotid artery occlusion or by ophthalmic artery occlusion, which gave a wide range of DO2. DO2 and MO2_1_Hr were evaluated based on three types of images: 1) red-free images to measure vessel diameters, 2) fluorescence images to estimate blood velocities by the displacement of intravascular fluorescent microspheres over time, and 3) phosphorescence images to quantify vascular oxygen tension from the phosphorescence lifetime of an intravascular oxygen sensitive phosphor. Loss of oxygen delivery (DO2L) was calculated as the difference between DO2 under normal/sham condition and DO2 during ischemia. AO2D, a volume of oxygen, was calculated as the product DO2L and T. Including all data, the linear relationship between AO2D and MO2_1_Hr was significant (R2 = 0.261, P = 0.0003). Limiting data to that in which T or DO2L was maximal also yielded significant relationships, and revealed that DO2L at a long duration of ischemia contributed disproportionately more than T to MO2_1_Hr. We discuss the potential of AO2D for quantifying the ischemic retinal insult, predicting the ischemic retinal injury and evaluating the likelihood of infarction.

The long and short of mistress relationships: Sex-differentiated mate preferences reflect a compromise of mating ideals.

OBJECTIVE: Evolved mate preferences have taken center stage in evolutionary psychology research, yet this literature has been fairly muted on mate preferences for extrapair partners. Here, we examined the mate preferences for mistress relationships (the traits that men prioritize in a mistress and mistresses prioritize in their male partners) and compared these preferences to those of short- and long-term relationships. METHOD: In two studies (NStudy 1a  = 104, NStudy 1b  = 191), we derived dimensions of mate preferences through exploratory factor analyses. In subsequent studies (NStudy 2  = 219, NStudy 3  = 101), we employed a budget allocation paradigm, where participants designed their ideal mates for different relationship types (short-term, long-term, and mistress relationships). RESULTS: Whereas men focused on fulfilling short-term mating ideals (by prioritizing physical attractiveness) in a mistress relationship, women focused on fulfilling long-term (but also some short-term) mating ideals (prioritizing both physical attractiveness and social status) for a mistress relationship. CONCLUSION: Findings indicate that mistress relationships reflect a compromise of men's and women's (conflicting) mating ideals and contribute to an understanding of relationships that are neither completely short- nor long-term in nature.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

The decreased PG content of pgp1 inhibits PSI photochemistry and limits reaction center and light-harvesting polypeptide accumulation in response to cold acclimation.

MAIN CONCLUSION: Decreased PG constrains PSI activity due to inhibition of transcript and polypeptide abundance of light-harvesting and reaction center polypeptides generating a reversible, yellow phenotype during cold acclimation of pgp1. Cold acclimation of the Arabidopsis pgp1 mutant at 5 °C resulted in a pale-yellow phenotype with abnormal chloroplast ultrastructure compared to its green phenotype upon growth at 20 °C despite a normal cold-acclimation response at the transcript level. In contrast, wild type maintained its normal green phenotype and chloroplast ultrastructure irrespective of growth temperature. In contrast to cold acclimation of WT, growth of pgp1 at 5 °C limited the accumulation of Lhcbs and Lhcas assessed by immunoblotting. However, a novel 43 kD polypeptide of Lhcb1 as well as a 29 kD polypeptide of Lhcb3 accumulated in the soluble fraction which was absent in the thylakoid membrane fraction of cold-acclimated pgp1 which was not observed in WT. Cold acclimation of pgp1 destabilized the Chl-protein complexes associated with PSI and predisposed energy distribution in favor of PSII rather than PSI compared to the WT. Functionally, in vivo PSI versus PSII photochemistry was inhibited in cold-acclimated pgp1 to a greater extent than in WT relative to controls. Greening of the pale-yellow pgp1 was induced when cold-acclimated pgp1 was shifted from 5 to 20 °C which resulted in a marked decrease in excitation pressure to a level comparable to WT. Concomitantly, Lhcbs and Lhcas accumulated with a simultaneous decrease in the novel 43 and 29kD polypeptides. We conclude that the reduced levels of phosphatidyldiacylglycerol in the pgp1 limit the capacity of the mutant to maintain the structure and function of its photosynthetic apparatus during cold acclimation. Thus, maintenance of normal thylakoid phosphatidyldiacylglycerol levels is essential to stabilize the photosynthetic apparatus during cold acclimation.

A constitutive stress response is a result of low temperature growth in the Antarctic green alga Chlamydomonas sp. UWO241.

The Antarctic green alga Chlamydomonas sp. UWO241 is an obligate psychrophile that thrives in the cold (4-6°C) but is unable to survive at temperatures ≥18°C. Little is known how exposure to heat affects its physiology or whether it mounts a heat stress response in a manner comparable to mesophiles. Here, we dissect the responses of UWO241 to temperature stress by examining its growth, primary metabolome and transcriptome under steady-state low temperature and heat stress conditions. In comparison with Chlamydomonas reinhardtii, UWO241 constitutively accumulates metabolites and proteins commonly considered as stress markers, including soluble sugars, antioxidants, polyamines, and heat shock proteins to ensure efficient protein folding at low temperatures. We propose that this results from life at extreme conditions. A shift from 4°C to a non-permissive temperature of 24°C alters the UWO241 primary metabolome and transcriptome, but growth of UWO241 at higher permissive temperatures (10 and 15°C) does not provide enhanced heat protection. UWO241 also fails to induce the accumulation of HSPs when exposed to heat, suggesting that it has lost the ability to fine-tune its heat stress response. Our work adds to the growing body of research on temperature stress in psychrophiles, many of which are threatened by climate change.

Impairments of retinal hemodynamics and oxygen metrics in ocular hypertension-induced ischemia-reperfusion.

Ischemia-reperfusion (I/R) is an established model for retinal neurodegeneration. However, there is limited knowledge of retinal physiological metrics and their relationships to retinal function and morphology in the I/R model. The purpose of the study was to test the hypotheses that retinal hemodynamic and oxygen metrics are impaired and associated with visual dysfunction, retinal thinning, and retinal ganglion cell (RGC) loss due to I/R injury. Intraocular pressure (IOP) was increased in one eye of 10 rats for 90 min followed by reperfusion. Fellow eyes served as controls. After one week of reperfusion, multimodal imaging was performed to quantify total retinal blood flow (TRBF) and retinal vascular oxygen contents. Retinal oxygen delivery (DO2) and metabolism (MO2) were calculated. Pattern-evoked electroretinography (PERG) and optical coherence tomography were performed to measure RGC function and retinal thicknesses, respectively. RGCs were counted from retina whole mounts. After one week of reperfusion, TRBF was lower in study eyes than in control eyes (p < 0.0003). Similarly, DO2 and MO2 were reduced in study eyes compared to control eyes (p < 0.003). PERG amplitude, TRT, IRT, ORT, and RGCs were also lower in study eyes (p ≤ 0.01). DO2 and MO2 were correlated with PERG amplitude, TRT, IRT, and ORT (r ≥ 0.6, p ≤ 0.005). The findings improve knowledge of physiological metrics affected by I/R injury and have the potential for identifying biomarkers of injury and outcomes for evaluating experimental treatments.

Family still matters: Human social motivation across 42 countries during a global pandemic.

The COVID-19 pandemic caused drastic social changes for many people, including separation from friends and coworkers, enforced close contact with family, and reductions in mobility. Here we assess the extent to which people's evolutionarily-relevant basic motivations and goals-fundamental social motives such as Affiliation and Kin Care-might have been affected. To address this question, we gathered data on fundamental social motives in 42 countries (N = 15,915) across two waves, including 19 countries (N = 10,907) for which data were gathered both before and during the pandemic (pre-pandemic wave: 32 countries, N = 8998; 3302 male, 5585 female; M age  = 24.43, SD = 7.91; mid-pandemic wave: 29 countries, N = 6917; 2249 male, 4218 female; M age  = 28.59, SD = 11.31). Samples include data collected online (e.g., Prolific, MTurk), at universities, and via community sampling. We found that Disease Avoidance motivation was substantially higher during the pandemic, and that most of the other fundamental social motives showed small, yet significant, differences across waves. Most sensibly, concern with caring for one's children was higher during the pandemic, and concerns with Mate Seeking and Status were lower. Earlier findings showing the prioritization of family motives over mating motives (and even over Disease Avoidance motives) were replicated during the pandemic. Finally, well-being remained positively associated with family-related motives and negatively associated with mating motives during the pandemic, as in the pre-pandemic samples. Our results provide further evidence for the robust primacy of family-related motivations even during this unique disruption of social life.

Temperature stress in psychrophilic green microalgae: Minireview.

Photosynthetic algae are the main primary producers in polar regions, form the basis of polar food webs, and are responsible for a significant portion of global carbon fixation. Many cold-water algae are psychrophiles that thrive in the cold but cannot grow at moderate temperatures (≥20°C). Polar regions are at risk of rapid warming caused by climate change, and the sensitivity of psychrophilic algae to rising temperatures makes them, and the ecosystems they inhabit, particularly vulnerable. Recent research on the Antarctic psychrophile Chlamydomonas priscuii, an emerging algal model, has revealed unique adaptations to life in the permanent cold. Additionally, genome sequencing of C. priscuii and its relative Chlamydomonas sp. ICE-L has given rise to a plethora of computational tools that can help elucidate the genetic basis of psychrophily. This minireview summarizes new advances in characterizing the heat stress responses in psychrophilic algae and examines their extraordinary sensitivity to temperature increases. Further research in this field will help determine the impact of climate change on psychrophiles from threatened polar environments.

When intelligence hurts and ignorance is bliss: Global pandemic as an evolutionarily novel threat to happiness.

INTRODUCTION: The savanna theory of happiness posits that it is not only the current consequences of a given situation that affect happiness but also its ancestral consequences, and that the effect of ancestral consequences on happiness is stronger among less intelligent individuals. But what about situations that did not exist in the ancestral environment and thus have no ancestral consequences? Global pandemic is one such situation that has no ancestral analog, and the theory predicts such evolutionarily novel threats to have a negative effect disproportionately on the life satisfaction of more intelligent individuals. METHODS: We analyzed prospectively longitudinal data from population samples from the National Child Development Study (Study 1) and the British Cohort Study (Study 2). RESULTS: Consistent with the theoretical prediction, while more intelligent individuals were generally more satisfied with their lives than less intelligent individuals were throughout adulthood (albeit not because they were more intelligent but because they earned more money, were more likely to be married, and healthier), more intelligent individuals were less satisfied with their lives during the COVID-19 global pandemic because they were more intelligent. CONCLUSION: Higher intelligence may have a downside in the modern world, by allowing life satisfaction to be more vulnerable from being better able to comprehend the severity of problems that did not exist in the ancestral world.

Looks and status are still essential: Testing the mate preference priority model with the profile-based experimental paradigm.

OBJECTIVE: Although the mate preference priority model (MPPM) has advanced our understanding of mate preferences, tests of the MPPM have relied on methods using text labels and thus lack ecological validity. We address this gap by testing the MPPM using J. M. Townsend's profile-based experimental paradigm, which utilizes profiles comprising photos of pre-rated models to manipulate physical attractiveness as well as costumes and descriptions to manipulate social status. METHOD: Using Singaporean samples, we conducted two studies (Study 1 n = 431, Study 2 n = 964) where participants judged the short-term and long-term mating desirability of opposite-sex profiles varying systematically on physical attractiveness and social status. We also tested whether treating these attributes as ordinal or continuous variables would be more valid. RESULTS: Results showed broad support for evolutionary predictions of mate preferences and priorities while revealing an increased premium placed on social status in our sample. We also found that continuous operationalizations produced less inflated results. CONCLUSIONS: The current research provides the first non-label, profile-based test of the MPPM, a well-powered replication of the profile-based paradigm, and an opportunity to observe the robustness and variations of mate preferences in a non-Western culture.

Sunshine on my shoulders makes me happy. . . especially if I'm less intelligent: how sunlight and intelligence affect happiness in modern society.

The savanna theory of happiness proposes that, due to evolutionary constraints on the human brain, situations and circumstances that would have increased our ancestors' happiness may still increase our happiness today, and those that would have decreased their happiness then may still decrease ours today. It further proposes that, because general intelligence evolved to solve evolutionarily novel problems, this tendency may be stronger among less intelligent individuals. Because humans are a diurnal species that cannot see in the dark, darkness always represented danger to our ancestors and may still decrease our happiness today. Consistent with this prediction, the analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data shows that exposure to sunlight was associated with happiness but the association was significantly weaker among more intelligent individuals.

Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.

Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5-79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7-50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9-18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0-0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06-1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06-8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

Champions of winter survival: cold acclimation and molecular regulation of cold hardiness in evergreen conifers.

Evergreen conifers are champions of winter survival, based on their remarkable ability to acclimate to cold and develop cold hardiness. Counterintuitively, autumn cold acclimation is triggered not only by exposure to low temperature, but also by a combination of decreasing temperature, decreasing photoperiod and changes in light quality. These environmental cues control a network of signaling pathways that coordinate cold acclimation and cold hardiness in overwintering conifers, leading to cessation of growth, bud dormancy, freezing tolerance and changes in energy metabolism. Advances in genomic, transcriptomic and metabolomic tools for conifers have improved our understanding of how trees sense and respond to changes in temperature and light during cold acclimation and the development of cold hardiness, but there remain considerable gaps deserving further research in conifers. In the first section of this review, we focus on the physiological mechanisms used by evergreen conifers to adjust metabolism seasonally and to protect overwintering tissues against winter stresses. In the second section, we review how perception of low temperature and photoperiod regulate the induction of cold acclimation. Finally, we explore the evolutionary context of cold acclimation in conifers and evaluate challenges imposed on them by changing climate and discuss emerging areas of research in the field.

Assessment of retinal oxygen metabolism, visual function, thickness and degeneration markers after variable ischemia/reperfusion in rats.

After total retinal ischemia induced experimentally by ophthalmic vessel occlusion followed by reperfusion, studies have reported alterations in retinal oxygen metabolism (MO2), delivery (DO2), and extraction fraction (OEF), as well as visual dysfunction and cell loss. In the current study, under variable durations of ischemia/reperfusion, changes in these oxygen metrics, visual function, retinal thickness, and degeneration markers (gliosis and apoptosis) were assessed and related. Additionally, the prognostic value of MO2 for predicting visual function and retinal thickness outcomes was reported. Sixty-one rats were divided into 5 groups of ischemia duration (0 [sham], 60, 90, 120, or 180 min) and 2 reperfusion durations (1 h, 7 days). Phosphorescence lifetime and blood flow imaging, electroretinography, and optical coherence tomography were performed. MO2 reduction was related to visual dysfunction, retinal thinning, increased gliosis and apoptosis after 7-days reperfusion. Impairment in MO2 after 1-h reperfusion predicted visual function and retinal thickness outcomes after 7-days reperfusion. Since MO2 can be measured in humans, findings from analogous studies may find value in the clinical setting.

Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration.

The retinal degeneration 1 (rd1) mouse is a well-established model of inherited retinal degeneration, displaying photoreceptor degeneration and retinal vasculature damage. The purpose of the current study was to determine alterations in the rate of oxygen delivery from retinal circulation (DO2), the rate of oxygen extraction from the retinal circulation for metabolism (MO2), and oxygen extraction fraction (OEF) in rd1 mice. The study was performed in a total of 18 wild type (WT) and 10 rd1 mice at both 3-weeks and 12-weeks of age. Retinal arterial and venous oxygen contents (O2A and O2V) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO2 and MO2 were determined as TRBF × O2A and TRBF × (O2A-O2V), respectively. OEF was calculated as MO2/DO2. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO2 and MO2 were lower in rd1 mice compared to WT mice (P ≤ 0.001), whereas OEF was not significantly different between rd1 and WT mice (P = 0.4). TRBF and DO2 were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO2 was not significantly different between age groups (P = 0.4) and OEF was higher at 3-weeks of age compared to 12-weeks of age (P = 0.003). Additionally, the outer and inner retinal cell layer thicknesses were decreased in rd1 mice at 12-weeks of age compared to both age-matched WT mice and rd1 mice at 3-weeks of age (P ≤ 0.02). MO2 was directly correlated with both IR and TR thickness (R ≥ 0.50; P ≤ 0.03, N = 20). The findings indicate that the rate oxygen is supplied by the retinal circulation is decreased and the reduction in oxygen extracted for metabolism is related to retinal cell layer thinning in rd1 mice.