Biology subjects

Yu, J.

Publications and source records attributed to Yu, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Glycogen removal enhances ethylene production in Synechocystis sp. PCC 6803 but exposes a 2-oxoglutarate-GS-GOGAT-phosphate constraint

Cyanobacteria are promising platforms for converting CO2 directly into value-added chemicals. However, redirecting fixed carbon toward a product requires understanding of how cells balance the energetic and redox supplies and demands - and how efficiently metabolic flux can be channelled into product formation rather than being dissipated or excreted. Glycogen, synthesized via ADP-glucose pyrophosphorylase (GlgC), is the major native carbon and energy sink, and its removal forces cells to redirect excess carbon and reducing power into alternative pathways. As a target product we used ethylene, a major industrial building block currently derived almost entirely from fossil feedstocks, which can be produced photoautotrophically by the ethylene-forming enzyme (EFE) at the expense of 2-oxoglutarate (2-OG), a central node linking carbon and nitrogen metabolism. Here, we compared wild-type Synechocystis sp. PCC 6803 with strains carrying either a complete ({Delta}glgC) or attenuated, light-responsive (LGS; psbA2-driven glgC) glycogen synthesis block, with an EFE-expressing strain (EFE), and with the combined {Delta}glgC+EFE strain. All strains were cultivated across a light gradient (35-300 mol photons m-2 s-1) under nitrogen-replete conditions. Integrating measurements of growth and ethylene production rates, chlorophyll-fluorescence analysis, quantitative proteomics, FTIR profiling, and overflow-metabolite analysis revealed that partial suppression of glycogen synthesis (LGS) enhanced growth under low irradiance but became detrimental above a critical light threshold. EFE expression in the {Delta}glgC background increased ethylene production in a light-dependent manner but further compromised growth. Both strains with EFE increased photosynthetic electron transport consistent with the carbon-sink effect, yet this electron surplus was not channelled proportionally into product or biomass. Instead, continuous 2-OG drain by EFE constrained flux through the GS-GOGAT node and induced a secondary inorganic phosphate limitation in {Delta}glgC+EFE that activated photoprotection and limited productivity. These results point to the 2-OG/GS-GOGAT/Pi axis as a key design constraint determining whether the surplus photosynthetic flux gets converted into product, dissipated through photoprotection, or released as overflow metabolites.

plant biology↗

bioRxiv2026

Early Prenatal Cell-Free DNA Methylation Landscape Informs Epigenetic Purification of the Circulating Fetal Genome

Circulating fetal cfDNA is the analyte of a screening test used by millions of pregnant women annually. However, low fetal fraction limits current testing. Fetal cfDNA can be enriched via hypomethylation, but the informative sites require a first-trimester fetal methylome reference. Here we sequenced fetal cfDNA (median purity 94.7%) derived from discarded media from cultured chorionic villus biopsies (n=30) and assembled a first-trimester methylome across 26M CpG methylation sites at a median depth of 207x. We then built an analytical enrichment model that identified millions of CpG markers and assigned predicted enrichment scores. Guided by this model, we adapted epiSIFT as a genome-wide assay selective for unmethylated DNA molecules. In 28 prenatal plasma cases, epiSIFT raised the median fetal fraction from 5.1% to 28.4% (5.6-fold gain) using the top eighth of markers. These findings establish a first-trimester fetal cfDNA methylome reference and demonstrate epigenetic enrichment of the fetal genome.

genomics↗

bioRxiv2026

Early-life core microbiota are associated with postlarval survival of Penaeus vannamei: A meta-analysis

Larviculture is critical to the production of Penaeus vannamei, the world's leading farmed shrimp species, but remains constrained by erratic postlarval survival. Although early-life microbiome establishment is increasingly recognized as essential for larval health and survival, microbiome-based hatchery interventions are hindered by limited understanding of larval core microbiota. Here, we synthesized publicly available and self-generated 16S rRNA gene amplicon datasets of larval and rearing-water microbiota from 13 studies encompassing seven major producing regions worldwide to characterize shrimp larval core microbiota, their assembly processes, and their associations with larval survival. Although larval prokaryotic communities exhibited stronger geographic variation than developmental-stage succession, a conserved set of dominant bacterial families, including Roseobacteraceae, Vibrionaceae, Flavobacteriaceae, Moraxellaceae, and Pseudoalteromonadaceae, consistently prevailed across developmental stages and regions. By integrating occupancy, persistence, and ecological network centrality analyses, we demonstrated that common, temporal, and ecological core microbiota differ substantially in composition, diversity, stage specificity, and ecological roles in network stability. Compared with non-core taxa, core taxa were generally assembled more deterministically, irrespective of core category, suggesting stronger host selection and/or more rapid dispersal during microbiome establishment. Core microbiota also generally showed stronger associations with postlarval survival than total communities or non-core taxa, although contrasting survival associations among core members indicated that core microbiota are not ecologically homogeneous. Our work provides the first systematic categorization and characterization of larval core microbiota throughout the shrimp larviculture cycle, offering new insights into the ecological significance of core microbiota and identifying potential universal targets for microbiome-based intervention in shrimp larviculture.

microbiology↗

bioRxiv2026

De novo design of metalloenzymes using Metal Mer

De novo enzyme design provides a route to create biocatalysts for target reactions, yet achieving high activity and selectivity directly from computation remains challenging. How best to design catalytic sites remains an open question, and enzyme design-metalloenzyme design for new-to-nature transformations in particular-is still limited in success rate, in substrate scope, and in the range of reactions accessible. Here we present a pipeline that produces efficient metalloenzymes directly from computation. It uses Metal Mer, a structural unit mapping backbone geometry to statistically preferred metal coordination modes, to build metal-binding sites with high confidence, and then constructs the catalytic core around the reaction product with geometric restrictions. Using the pipeline, we designed zinc-dependent hydride-transfer enzymes, obtaining a highly selective variant that exhibits enantiomeric excess (ee) >99% on 13 substrates without directed evolution. For steroid substrates bearing multiple carbonyl groups, redesigned variants achieved high regio- and diastereo- selectivity greater than 19:1. Applying this framework to iron-catalyzed alkene difunctionalization, designed variants were active out of the box (10% yield, 70:30 enantiomeric ratio (e.r.)), exceeding a previously reported natural functional analogs (<5% yield, <60:40 e.r.); a single active-site residue mutation further raised selectivity to 96:4 e.r. for several substrates, on par with extensively evolved natural enzymes. The crystal structure of an active design matches the computational model with a backbone RMSD of 0.4 Angstrom, supporting the accuracy of the approach. These results establish our design framework as a general strategy for the de novo design of metalloenzyme series with diverse coordination geometries and coordinating residues, enabling efficient and selective catalysis of challenging chemical transformations.

synthetic biology↗

bioRxiv2026

Engineering potent avian GPR25 agonists using an ostrich CXCL17 gene relic

C-X-C motif chemokine ligand 17 (CXCL17) activates G protein-coupled receptor 25 (GPR25) in most vertebrate lineages. Although birds appear to have lost functional CXCL17, CXCL17 gene relics and intact GPR25 genes persist in certain taxa. This study investigated whether a fragment encoded by an avian CXCL17 gene relic could guide the engineering of potent agonists for avian GPR25s. A 22-residue C-terminal fragment encoded by African ostrich CXCL17 gene relic was grafted onto the corresponding position of loggerhead turtle or human CXCL17, and the resulting hybrids were prepared via bacterial overexpression and functionally characterized via cell-based assays. The turtle-ostrich and human-ostrich CXCL17 hybrids showed no detectable activity at turtle or human GPR25 but exhibited substantially greater potency than their parental proteins at two avian GPR25s in {beta}-arrestin recruitment assays, with half-maximal effective concentrations of approximately 25 and 100 nM at the ostrich receptor and 5 and 13 nM at the mallard receptor, respectively. Both hybrids bound directly to the ostrich or mallard GPR25 in homogenous ligand-receptor binding assays and induced migration of transfected cells expressing the ostrich or mallard receptor in chemotaxis assays. These findings demonstrate that a fragment encoded by the ostrich CXCL17 gene relic confers potent avian GPR25 agonism and establishes the C-terminus as the primary driver of species selectivity. These hybrids provide functional surrogate tools for probing avian GPR25 biology.

biochemistry↗

bioRxiv2026

Keratinocyte FABP5 mediates saturated fat-induced MAPK/CCL20 signaling in psoriatic inflammation

Saturated fats in high-fat diets (HFDs) have been associated with increased risk and severity of psoriasis. However, the underlying cellular and molecular mechanisms remain to be further defined. Here, using a unique mouse strain with keratinocyte-specific deletion of fatty acid-binding protein 5 (FABP5) (Fabp5f/fKrt6a-Cre), we reported that keratinocyte FABP5 deletion significantly attenuated saturated HFD-exacerbated psoriatic symptoms. Immunological analyses demonstrated that FABP5 specific deletion in keratinocytes selectively reduced skin TCR {gamma} {delta} dim cell accumulation and IL-17A production. Further skin bulk-RNA and single-cell RNA sequence analyses showed a strong association of keratinocyte FABP5 with increased activation of mitogen-activated protein kinase (MAPK) pathways under saturated HFD-induced obesity. Mechanistically, saturated fatty-acids (SFAs) induce FABP5-dependent MAPK activation and CCL20 production in keratinocytes, promoting the recruitment and activation of IL-17-producing {gamma}{delta} T cells in the skin. Together, these findings suggest a previously undefined FABP5/MAPK/CCL20 signaling axis that links saturated fats to exacerbated psoriatic inflammation.

immunology↗

bioRxiv2026

Circadian phase alignment promotes survival under predictive oxidative stress

Circadian clocks are endogenous time-keeping mechanisms that continue to oscillate with a period that approximates 24 h in the absence of cyclic environmental cues. This free-running period (FRP) varies from species to species and can vary within species across latitudinal clines. Because natural environments provide daily cues that reset circadian clocks to exactly 24 h, the importance of the FRP length is unclear. Using the cyanobacterium Synechococcus elongatus we show that the FRP length alters the alignment of a biological process with an environmental reference, known as phase angle of entrainment, across seasonal photoperiods, thereby repositioning stress response programs relative to the external environment. This phase relationship affects the overall fitness of the organism: strains that position stress-response programs to peak at the time at which the stressor peaks outcompete their early- or late-peaking counterparts. Our results suggest that the FRP length is selected for its ability to adjust the phase angle of entrainment across seasonal photoperiods: the wild-type FRP length was uniquely plastic in its ability to adjust stress-response programs to coincide with the stressor in all photoperiod conditions.

microbiology↗

bioRxiv2026

Restoration of deficient IL-15 signaling enhances innate lymphoid cell immunity in brain metastasis

Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s), collectively known as group 1 innate lymphoid cells (ILCs), are critical mediators of anti-tumor immunity, yet their role in brain metastasis remains poorly defined. Using single-cell RNA sequencing and functional depletion models, we show that group 1 ILCs fail to provide adequate tumor control in breast cancer brain metastasis (BCBM). In contrast to the liver, where diverse, functionally competent group 1 ILC populations facilitate excellent metastatic control, group 1 ILCs in BCBM show limited diversity and profound tissue-specific dysfunction such that their depletion had no effect on tumor burden despite modest parenchymal infiltration. We attribute this group 1 ILC dysfunction to severely restricted IL-15 availability, with IL-15R protein detected at 500-fold lower concentration in the brain than in the liver. Local IL-15 complex administration restored group 1 ILC accumulation, cytotoxicity, and tissue residency, significantly reducing brain metastatic burden independent of T cells. Intracranial delivery of IL-15-secreting induced pluripotent stem-cell-derived (iPSC)-NK cells, already in clinical testing for non-small cell lung cancer, significantly reduced tumor burden. Collectively, these findings reveal how tissue-specific differences in cytokine availability shape group 1 ILC population diversity and disease response, establishing localized IL-15 signaling as a compelling strategy to unlock innate immunity against intracranial malignancies.

immunology↗

bioRxiv2026

Rational Design of 5' UTRs for Optimized mRNA Expression and Cost-Effective, Rapid Analysis of Capped mRNA

In vitro-transcribed (IVT) messenger RNA (mRNA) therapeutics require rigorous quality control of 5' capping efficiency and 3' poly(A) tail length, both of which constitute critical quality attributes (CQAs). Current analytical workflows for these CQAs rely on hybridization with nucleic acid probes and biotin-based affinity purification, which constrain throughput and increase per-assay cost. Here, we report a rationally designed 5' untranslated region (5' UTR) that sustains high translational efficiency while enabling probe-free, one-step purification for rapid quantification of capping efficiency and poly(A) tail length distribution. This approach exploits a strategically engineered 5' UTR incorporating a purine-only RNase A-resistant fragment terminating at a single pyrimidine cleavage site, together with a translation-enhancing element comprising an N6-methyladenosine (m6A) deposition motif and an 18S rRNA complementarity sequence. This dual-function design accommodates GA-rich sequence segments without compromising mRNA translational output. Compared with conventional probe- and biotin-dependent workflows, the present method substantially reduces cost and processing time and is compatible with simultaneous detection of segmented AmGn poly(A) tail variants. This integrated platform provides a simplified, probe-free and construct-universal for high-throughput in-process control (IPC) of mRNA therapeutics.

bioengineering↗

bioRxiv2026

The fusion gene occurrence spectrum predicts the spatial structure of chromosomes

Chromosome was "self-assembled" into a complex three-dimensional topology in the nucleus, which provided the structural basis for important biological processes such as gene expression regulation and cell differentiation. The current understanding of the three-dimensional organization of the genome is based on high-throughput sequencing and imaging technologies to visualize the conformation of chromatin in its native environment. This study proposes a new research perspective and technical means to use fusion genes to determine the interaction information and three-dimensional structure of chromosomes. This three-dimensional information provided by the fusion gene spectrum not only shows the universality of the spatial layout of chromosomes, but also increases the interpretability of the occurrence of fusion genes. The chromatin conformation capture data of multiple tissues and periods is significantly correlated with the strength of fusion genes. For example, the frequency of trans-interaction between chromosomes 11 and 17 was the highest, and the frequency of fusion gene occurrence corresponding to KMT2A on chromosome 11 was the highest. Therefore, we infer that this structural universality is a common feature of the human genome, which provides a theoretical basis and data for predicting chromosome fusion events.

cancer biology↗

bioRxiv2026

A Bispecific Biologic That Robustly Reverses HIV-1 and SIV Latency

Antiretroviral therapy suppresses HIV-1 replication but cannot eliminate the latent viral reservoir persisting in memory CD4 T cells. Existing latency reversal candidates have yet to achieve robust viral reactivation at tolerable doses. We engineered T4IL15{triangleup}, a bispecific biologic that selectively delivers IL-15 signaling to memory CD4 T cells, with minimal off-target stimulation. T4IL15{triangleup} reactivated latent virus in 94% (48/51) of clinical samples ex vivo, 75% (15/20) of administrations in HIV-1-infected and ART-suppressed humanized mice, and 100% (6/6) of SIV-infected and ART-suppressed rhesus macaques at doses well tolerated. We also found that off-target stimulation of non-CD4 cells hindered HIV-1 reactivation ex vivo. T4IL15{triangleup} provides a robust reactivation platform that could complement other reservoir-elimination strategies toward an HIV-1 cure.

microbiology↗

bioRxiv2026

PGG Enhances Olaparib Efficacy via cGAS-STING Signaling and Sensitizes Triple-Negative Breast Cancer to PD- L1 Blockade

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy and options for targeted therapy are limited. Although PARP inhibitors (PARPi) like olaparib (Ola) leverage synthetic lethality, their clinical utility is severely impeded by drug resistance and low frequency of BRCA mutations. In this study, 1,2,3,4,6-penta-O-galloyl-{beta}-D-glucose (PGG), a natural polyphenolic compound, can induce a state of homologous recombination deficiency (HRD) in TNBC cells by inhibiting the PALB2-BRCA2 interaction. PGG potentiated the inhibitory effects of Ola on the in vitro proliferation, clonogenic potential, migration, and invasion of TNBC cells. Mechanistically, the dual therapy triggered severe oxidative stress and mitochondrial collapse, which accelerated the classical apoptosis cascade and promoted the emission of immunogenic cell death (ICD)-associated DAMPs. The accumulated cytosolic double-stranded DNA activated the innate immune cGAS-STING pathway, thereby promoting robust intra-tumoral infiltration of CD8+ T cells. Furthermore, since cGAS-STING hyperactivation drives compensatory PD-L1 upregulation on TNBC cells, incorporating anti-PD-L1 antibody into the combination regimen further reversed the immunosuppressive barrier, achieving near-complete tumor eradication and maximum infiltration of cytotoxic T cells in vivo. Bioinformatics analyses further suggested a potential network of PGG targets associated with extracellular matrix organization, offering a bioinformatics-derived hypothesis for its theoretical involvement in modulating stromal tension and vascular homeostasis. Collectively, this study establishes PGG as a multi-functional therapeutic agent integrating intracellular synthetic lethality and innate immune sensing, while providing a preliminary bioinformatic rationale for prospective microenvironmental investigation. This study also shows PGG as a multi-functional therapeutic agent that integrates intracellular synthetic lethality, innate immune sensing, and microenvironmental remodeling to convert immunologically "cold" TNBC into "hot" tumors.

biochemistry↗

bioRxiv2026

SubCortexMesh: A Python toolbox for surface-based analysis of subcortical brain regions

Neuroimaging research focusing on subcortical brain regions showed that they play a role in a wide range of cognitive functions and associated their structural alterations to various psychiatric disorders. Methods to analyse such structures were developed to observe changes, not simply in terms of volumes, but in terms of surfaces, which are able to detect subtle and local changes in shape and geometrical configuration. Such advanced analyses have however been largely restricted to command line environments with relatively limited access to Python users or researchers with low technical expertise. We present SubCortexMesh as a user-friendly toolbox which covers automated surface estimation from popular subcortical volume segmentations (FreeSurfer and the Functional Magnetic Resonance Imaging of the Brain Software Library (FSL)), computes shape-related vertex-wise metrics (thickness, surface area and curvature) for whole cohorts and includes statistical analyses. This is all done inside Python, automatically computing all subjects of a given preprocessed directory, with the explicit intent to minimise steps and manual coding required from the users. SubCortexMesh includes statistical tools which allow conventional random field theory-based cluster analyses on native subject metrics, standardised within common surface templates, thus containing a whole workflow necessary to run an up-to-date shape-wise subcortical analyses in one package.

neuroscience↗

bioRxiv2026

Restoring multiple TDP-43 cryptic targets, but not solely Unc13a, rescues motor neuron disease

Dysfunction of TAR DNA-binding protein 43kDa (TDP-43) underlies amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder with limited therapeutic options. While current therapeutic approaches are designed to individually target unique cryptic exons of TDP-43 such as UNC13A, the sufficiency of such a strategy to mitigate motor neuron disease remains unclear. Using a mouse model lacking TDP-43 in spinal motor neurons which mimics early stages of ALS, we show that the exclusion of Unc13a cryptic exon fails to mitigate motor neuron disease. In contrast, the restoration of multiple TDP-43 cryptic targets, including Unc13a, attenuated motor neuron loss, and rescued motor neuron disease. Additionally, compared to brain neurons, spinal motor neurons accumulate markedly lower amounts of Unc13a cryptic exons in mice and humans, suggesting that the contribution of this TDP-43 cryptic target to spinal motor neuron loss may be limited. Together, these results strongly support ALS therapeutic strategies designed to simultaneously restore multiple TDP-43 cryptic targets to attenuate spinal motor neuron loss.

neuroscience↗

bioRxiv2026

Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer

Amygdala metabolic activity (AmygAc) measured by [18F]FDG PET has been associated with chronic psychological stress and adverse clinical outcomes, but its relationship with antitumor immunity and treatment response remains incompletely understood. We investigated AmygAc as a host-derived imaging biomarker in non-small cell lung cancer (NSCLC) and examined its association with survival, response to immune checkpoint inhibition (ICI), and the tumor immune microenvironment. Methods: In this multicenter retrospective study, baseline [18F]FDG PET scans from 256 treatment-naive patients with NSCLC were analyzed to quantify AmygAc. Overall survival was assessed in the full cohort, and treatment response was evaluated in 79 patients who subsequently received neoadjuvant ICI therapy. AmygAc was integrated with clinical and tumor-derived imaging parameters. To investigate its biological correlates, tumor tissue from a selected subcohort was analyzed using multiplex immunofluorescence and spatial transcriptomics.

cancer biology↗

bioRxiv2026

Cheetahs Combine Head Pitch Stabilisation with Predictive Yaw Tracking during High-speed Pursuit

Predators pursuing agile prey must coordinate locomotion with rapidly changing visual information, yet how they control head orientation during high-speed terrestrial pursuit remains poorly understood. We reconstructed three-dimensional head, torso, and lure target trajectories from synchronised multi-camera recordings of freely running cheetahs (Acinonyx jubatus) using model-based markerless reconstruction, and propagated reconstruction uncertainty through Monte Carlo analysis. Across 1,373 valid reconstructed pursuit frames, head pitch was more closely aligned with the target than torso pitch, and is tightly stabilised relative to target elevation. Head-on-torso counter-rotation nearly cancelled concurrent torso-pitch rotations, preserving target-relative head pitch despite locomotor oscillations. In yaw, cheetahs predominantly oriented their heads ahead of the target's instantaneous position while maintaining a distinct locomotor heading and continuing to close range. During steady-lateral pursuit, head yaw was best described by a short horizon constant-velocity extrapolation model with a cross-validated median prediction horizon of 45 ms. Together, these findings reveal complementary head orientation strategies during pursuit: robust sagittal stabilisation and predictive lateral tracking keep the head target-referenced while the torso generates a closing trajectory towards intersection.

animal behavior and cognition↗

bioRxiv2026

Transthyretin Contributes to Hippocampal Blood-Brain Barrier Recovery Following Intestinal Inflammation, with Reduced Expression in Alzheimer's Disease

Background: The blood-brain barrier (BBB) is increasingly recognized as an active immunoregulatory interface that responds dynamically to systemic inflammation. As intestinal inflammation can influence brain homeostasis through the gut-brain axis, the endogenous mechanisms that preserve BBB integrity during gut-derived inflammatory stress remain poorly understood. Methods and Results: We combined dextran sulfate sodium-induced colitis, fecal microbiota transplantation, aged mice, APP/PS1 mice, human Alzheimer's disease (AD) brain tissue, single-cell RNA sequencing, in vivo BBB permeability assays, and gain- and loss-of-function approaches to investigate adaptive neurovascular responses to gut inflammation and their mechanism in maintaining BBB integrity. Intestinal inflammation induced a region-specific adaptive response characterized by increased hippocampal vascular remodeling and partial restoration of BBB integrity following the initial inflammatory insult. Single-cell transcriptomic analysis identified a transthyretin (TTR)-enriched vascular-associated microglial state accompanying these neurovascular changes. Functional studies demonstrated that TTR contributes to maintaining BBB integrity by promoting endothelial homeostasis and limiting endothelial endocytosis, consistent with modulation of FcRn-associated transport pathways. This adaptive neurovascular response was progressively attenuated in aged mice and APP/PS1 mice and was accompanied by reduced vascular TTR expression in human AD brains. Conclusion: These findings identify TTR as a contributor of adaptive neurovascular homeostasis during gut-derived neuroinflammation. Impairment of this homeostatic response with aging and AD may contribute to persistent BBB dysfunction and chronic neuroinflammation, highlighting neurovascular resilience as a potential therapeutic target.

neuroscience↗

bioRxiv2026

A Translational Reference for Green Autofluorescence Imaging in the Rhesus Macaque Eye using the OcuMet Beacon

PurposeTo evaluate associations between green autofluorescence (GAF) and structural and functional measures relevant to retinal and optic neuropathies, and to establish normative GAF values across the optic nerve head (ONH), macula, and papillofoveal bundle (PFB) in rhesus macaques. MethodsEighty-two macaques with normal ONH morphology by spectral-domain optical coherence tomography (SD-OCT) were included with a mean {+/-} SD age of 12.76 {+/-} 7.18 (range 0.11-29.39) years. The GAF images were acquired in the ONH, macula and PFB with the OcuMet Beacon. In a subset of macaques (n=19), pattern electroretinogram (PERG) and photopic full-field ERG including the photopic negative response (PhNR) were recorded. ResultsThe GAF significantly increased with age in the ONH, macula and PFB. After adjusting by age, there were no sex differences, but IOP showed a positive association with macular GAF. At the ONH, higher GAF correlated with thinner retinal nerve fiber layer, inner and outer segment complex, and total retinal thickness. In the macula, inner nuclear layer thickness was positively associated with GAF, whereas outer plexiform layer and inner and outer segment complex were inversely associated. The PERG amplitudes inversely tracked ONH GAF. ConclusionsGAF rises with age and IOP, couples to retinal structure, and at the ONH, aligns with inner-retinal functional indices. This study provides a regional reference for GAF in rhesus macaques. Translational RelevanceNormative GAF data in healthy rhesus macaques provide a framework for interpreting this noninvasive signal in translational studies of retinal and optic nerve disease.

physiology↗