Article
Endocrinology & Metabolism
Christopher R. Starr, Assylbek Zhylkibayev, James A. Mobley, Marina S. Gorbatyuk
Summary: Diabetes, a metabolic disease, can lead to various health complications. Diabetic retinopathy (DR) affects millions of people worldwide and has complex mechanisms involving both neural and vascular components in the retina. This study identified changes in protein levels and O-glycosylation in the retinas of diabetic mice, providing important insights into the impact of diabetes on protein function and localization.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Ophthalmology
Anna Enzsoly, Rozina I. Hajdu, Zsolt Turoczi, Iren Szalai, Erika Tatrai, Fanni Palya, Zoltan Z. Nagy, Csaba Matyas, Attila Olah, Tamas Radovits, Klaudia Szabo, Bulcsu Dekany, Arnold Szabo, Akos Kusnyerik, Petra Soltesz, Daniel S. Veres, Aniko Somogyi, Gabor M. Somfai, Akos Lukats
Summary: The study found that an increased number of dual cones in diabetic rats correlated with fT4 levels. The risk of color vision deficiencies was higher in diabetic patients, but the study did not detect any effect of thyroid hormones on the development of color vision deficiencies.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Medicine, General & Internal
Alexandra Oltea Dan, Alin Stefanescu-Dima, Andrei Teodor Balasoiu, Ileana Puiu, Carmen Luminita Mocanu, Mihaela Ionescu, Andreea Cornelia Tanasie, Anca Elena Tartea, Veronica Sfredel
Summary: The purpose of this study is to identify and quantify preclinical changes in the retinal microcirculation of young type 1 diabetes patients. The results show significant differences in various retinal parameters between the T1D group and the control group. OCTA has the potential to be a valuable tool for early diagnosis in these patients.
Review
Medicine, General & Internal
Warren W. Pan, Thomas W. Gardner, Jennifer L. Harder
Summary: DRD remains a common cause of vision loss in working-age adults, with limited progress on new therapies due to the complexity of the human eye. Utilizing systems biology approaches that have been successful in DKD research may help clarify the molecular basis and progression of DRD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Ophthalmology
Feng Zhang, Zijing Du, Xiayin Zhang, Yaxin Wang, Yesheng Chen, Guanrong Wu, Yingying Liang, Dan Cao, Jun Zhao, Ying Fang, Jianhua Ma, Honghua Yu, Yijun Hu
Summary: This study investigated alterations in outer retinal reflectivity in diabetic patients without clinically detectable retinopathy. The results showed that the reflectivity was significantly lower in most retinal locations in these patients compared to controls. The reduction in outer retinal reflectivity was correlated with diabetes duration, HbA1c, and visual acuity. These findings suggest that the measurement of outer retinal reflectivity could potentially serve as a biomarker for early retinal alterations in diabetic patients.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Review
Neurosciences
Chengzhi Liu, Wenkang Dong, Zhengshuai Lv, Li Kong, Xiang Ren
Summary: Diabetic retinal neurodegeneration (DRN) occurs prior to retinal microvascular alterations and is associated with neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis. Thioredoxin-interacting protein (TXNIP) plays a significant role in DR and is involved in the regulation of multiple signaling pathways.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Maria H. Madeira, Ines P. Marques, Sonia Ferreira, Diana Tavares, Torcato Santos, Ana Rita Santos, Joao Figueira, Conceicao Lobo, Jose Cunha-Vaz
Summary: Diabetic retinopathy is not only a microvascular disease, but also involves neurodegeneration, with different phenotypes identified based on the characteristics of neurodegeneration. Understanding these phenotypes may offer insights for improved treatment and management of diabetic individuals with retinopathy.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Yanchao Xu, Yusong Zhang, Hongwei Liang, Xiaomeng Liu
Summary: This study found that CMS alleviated STZ-induced pathological changes in DR by activating SIRT1, including oxidative stress, inflammation, and cell apoptosis.
Article
Immunology
Kangjia Lv, Hui Ying, Guangyi Hu, Jing Hu, Qizhi Jian, Fang Zhang
Summary: This study used single-cell sequencing to identify microglia as the main source of IL-1 beta in STZ-induced DR mice. The findings suggest that activated microglia with metabolic alterations contribute to inflammation in the early stages of DR.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Jing Zhou, Bo Chen
Summary: Diabetic retinopathy (DR) is the most common microvascular complication in diabetes mellitus (DM) and is a leading cause of vision loss in working-age adults. Around 30% of diabetic individuals are affected by DR, and if left untreated, it can result in blindness. Recent studies have shown that DR causes early neuronal dysfunction and neurodegeneration, which may occur before vascular pathology and impact retinal neurons and glial cells. This new understanding has led to the development of therapeutic strategies aimed at preventing retinal neuronal dysfunction at the early stage of DR. Early detection and timely treatment to protect retinal neurons are crucial in preventing visual loss in DR.
Article
Biochemistry & Molecular Biology
Dongjoon Kim, Marcela Votruba, Sayon Roy
Summary: Reduced level of Opa1 promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy. Downregulation of Opa1 expression contributes to the development of retinal cell death and capillary damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Gen Miura
Summary: Visual evoked potentials (VEP) can detect visual pathway dysfunction in diabetes mellitus caused by abnormalities in blood glucose levels. Previous studies have shown that VEP can detect neuropathy before fundus examination and evaluate the correlation between VEP waveforms and disease duration, HbA1c, glycemic control, and short-term blood glucose fluctuations. VEP may be useful for predicting postoperative prognosis and assessing visual function in diabetic retinopathy. Further research with larger cohorts is needed to establish a more detailed relationship between diabetes mellitus and VEP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Michael Radzieta, Fatemah Sadeghpour-Heravi, Timothy J. Peters, Honghua Hu, Karen Vickery, Thomas Jeffries, Hugh G. Dickson, Saskia Schwarzer, Slade O. Jensen, Matthew Malone
Summary: This study investigated the host-microbe complex within DFIs using a multiomics approach, identifying Staphylococcus aureus and Streptococcus as abundant and highly active. Patients with severe DFIs demonstrated greater microbial diversity, enrichment of multispecies virulence genes, and significant differences in host response compared to mild to moderate DFIs.
NPJ BIOFILMS AND MICROBIOMES
(2021)
Article
Anatomy & Morphology
Zhiwei Xu, Shi Bai, Haijian Wu, Marong Fang
Summary: This study found that diabetic mice had elevated retinal RBP4 levels, and high levels of retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeneration.
MICROSCOPY RESEARCH AND TECHNIQUE
(2023)
Article
Neurosciences
Ahmed Dellaa, Sihem Mbarek, Rim Kahloun, Mohamed Dogui, Moncef Khairallah, Imane Hammoum, Narjess Ben Rayana-Chekir, Ridha Charfeddine, Pierre Lachapelle, Rafika Ben Chaouacha-Chekir
Summary: Monitoring the progression of diabetic retinopathy in Psammomys obesus showed a decrease in ERG components, abnormal vascular architecture, appearance of exudates, and significant reduction in retina thickness, reflecting clinical correlates of human DR in the diabetic animal model.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amanda L. Sharpe, Marta Trzeciak, Nicole L. Eliason, Harris E. Blankenship, Bre' Ana M. Byrd, Phillip D. Douglas, Willard M. Freeman, Michael J. Beckstead
Summary: The study reveals that the expression of GLAST and CRF2 in astrocytes in the SN/VTA is significantly affected by psychostimulant drugs, which may influence neurotransmission and related behaviors.
Article
Cell Biology
Bumsoo Ahn, Rojina Ranjit, Parker Kneis, Hongyang Xu, Katarzyna M. Piekarz, Willard M. Freeman, Michael Kinter, Arlan Richardson, Qitao Ran, Susan V. Brooks, Holly Van Remmen
Summary: The study aimed to determine the impact of mitochondrial hydrogen peroxide on muscle aging and contractile dysfunction. Results showed that muscle-specific overexpression of mPRDX3 can reduce mitochondrial H2O2 generation, improve mitochondrial function, and mitigate loss of muscle quantity and quality, despite the persistence of neuromuscular junction impairment.
Article
Neurosciences
Sarah R. Ocanas, Victor A. Ansere, Kyla B. Tooley, Niran Hadad, Ana J. Chucair-Elliott, David R. Stanford, Shannon Rice, Benjamin Wronowski, Kevin D. Pham, Jessica M. Hoffman, Steven N. Austad, Michael B. Stout, Willard M. Freeman
Summary: Common neurological disorders, such as Alzheimer's disease, multiple sclerosis, and autism, show significant sex differences in prevalence and clinical presentation. However, the role of sex differences in the brain is often overlooked in experimental models. This study used a mouse model to uncover the regulatory effects of sex chromosomes, independent of gonadal sex, on gene expression and DNA modification in the hippocampus.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Sarah R. Ocanas, Kevin D. Pham, Harris E. Blankenship, Adeline H. Machalinski, Ana J. Chucair-Elliott, Willard M. Freeman
Summary: Modern molecular and biochemical neuroscience studies often require the analysis of specific cellular populations derived from brain tissue samples. This is especially true for minority glial populations such as microglia, which may not be easily detected in whole tissue analyses. Mouse microglia were purified using different methods to compare their performance, with similar outcomes in terms of purity but differences in cell yield and isolation time. It was found that ex vivo activation signatures occurred during tissue dissociation and cell preparation, rather than the cell sorting process. The activation phenotype could be minimized by using inhibitors or conducting non-enzymatic dissociation at low temperatures. These findings suggest that a variety of microglial isolation approaches can be used depending on experimental needs, and inhibitors can effectively reduce cell preparation artifacts.
Article
Endocrinology & Metabolism
Samim Ali Mondal, Roshini Sathiaseelan, Shivani N. Mann, Maria Kamal, Wenyi Luo, Tatiana D. Saccon, Jose V. V. Isola, Frederick F. Peelor III, Tiangang Li, Willard M. Freeman, Benjamin F. Miller, Michael B. Stout
Summary: The naturally occurring diastereomer of 17β-estradiol, 17α-estradiol, can reduce liver fibrosis by suppressing hepatic stellate cell activation and enhancing collagen degradation mechanisms.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Neurosciences
Ana J. Chucair-Elliott, Sarah R. Ocanas, Kevin Pham, Michael Van der Veldt, Ashley Cheyney, David Stanford, Jami Gurley, Michael H. Elliott, Willard M. Freeman
Summary: Analysis of specific epigenetic and transcriptomic signatures in retina cell types is important for understanding retinal degenerative diseases. This study discovers a method to specifically analyze the epigenomes and translatomes of Muller glia cells. Applying this method to acute injury and chronic stress models reveals different transcriptomic changes in Muller glia cells for each stimulus.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Sarah R. Ocanas, Victor A. Ansere, Collyn M. Kellogg, Jose V. V. Isola, Ana J. Chucair-Elliott, Willard M. Freeman
Summary: Biological sex influences neurodegenerative diseases through genetic and hormonal mechanisms. Microglial reactivity and the pro-inflammatory environment of the aging brain are influenced by sex, age, and disease state. Further research is needed to understand the regulation of microglial sex effects and develop sex-informed prevention and treatment strategies for brain diseases.
BRAIN RESEARCH BULLETIN
(2023)
Article
Oncology
Sabira Mohammed, Nidheesh Thadathil, Phoebe Ohene-Marfo, Albert L. Tran, Michael Van Der Veldt, Constantin Georgescu, Sangphil Oh, Evan H. Nicklas, Dawei Wang, Nair Hariprasad Haritha, Wenyi Luo, Ralf Janknecht, Benjamin F. Miller, Jonathan D. Wren, Willard M. Freeman, Sathyaseelan S. Deepa
Summary: Blocking necroptosis reduces inflammation and hepatocellular carcinoma (HCC) in a mouse model of diet-induced HCC, particularly in male mice, suggesting necroptosis as a potential therapeutic target for NAFLD-mediated HCC.
MOLECULAR CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sarah R. Ocanas, Jose V. V. Isola, Tatiana D. Saccon, Kevin D. Pham, Ana J. Chucair-Elliott, Augusto Schneider, Willard M. Freeman, Michael B. Stout
Summary: Assessing cell-type-specific epigenomic and transcriptomic changes are key to understanding ovarian aging. The optimization of TRAP and INTACT methods were performed using a transgenic NuTRAP mouse model to study the ovarian transcriptome and epigenome in specific cell types.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Geriatrics & Gerontology
Michael B. B. Stout, Kelli L. L. Vaughan, Jose V. V. Isola, Shivani N. N. Mann, Bayli Wellman, Jessica M. M. Hoffman, Hunter L. L. Porter, Willard M. M. Freeman, Julie A. A. Mattison
Summary: Recent studies have shown that 17 alpha-estradiol can extend the healthspan and lifespan of male mice through multiple mechanisms, making it a potential candidate for translation into humans. However, there is currently no established dosing paradigm for the treatment of aging and chronic disease in humans. This study aimed to assess the tolerability of 17 alpha-estradiol treatment and evaluate metabolic and endocrine responses in male rhesus macaque monkeys during a short treatment period. The results showed that the dosing regimens were well-tolerated and had mild benefits on metabolic parameters, but significant feminization effects were observed.
Article
Immunology
Sarah R. Ocanas, Kevin D. Pham, Jillian E. J. Cox, Alex W. Keck, Sunghwan Ko, Felix A. Ampadu, Hunter L. Porter, Victor A. Ansere, Adam Kulpa, Collyn M. Kellogg, Adeline H. Machalinski, Manu A. Thomas, Zsabre Wright, Ana J. Chucair-Elliott, Willard M. Freeman
Summary: This study compared the transcriptome and translatome of hippocampal microglia between young and old mice and found sex differences in microglial gene expression. In old age, these differences were primarily female-biased and enriched in markers of senescence and disease. These findings may explain the differences in susceptibility and disease progression in Alzheimer's disease between males and females. Further studies are needed to explore the role of sex differences in microglial heterogeneity and the involvement of sex-specific regulators in response to Alzheimer's pathology.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Geriatrics & Gerontology
Victor A. Ansere, Matthew P. Bubak, Benjamin F. Miller, Willard M. Freeman
Summary: Experimental approaches like Heterochronic Plasma Transfer (HPT) are important tools for studying aging, but they have limitations and design challenges. This review provides insights into the considerations and caveats of HPT as a research tool, including plasma preparation, administration route, dosing regimen, and appropriate controls, to assist investigators in achieving their experimental goals.
REJUVENATION RESEARCH
(2023)
Article
Geriatrics & Gerontology
Collyn M. Kellogg, Kevin Pham, Adeline H. Machalinski, Hunter L. Porter, Harris E. Blankenship, Kyla B. Tooley, Michael B. Stout, Heather C. Rice, Amanda L. Sharpe, Michael J. Beckstead, Ana J. Chucair-Elliott, Sarah R. Ocanas, Willard M. Freeman
Summary: This study reveals that microglia are the primary source of MHC-I in mice and humans, with its expression increasing with aging and in Alzheimer's disease. The expression of Lilrs and Pilrs, MHC-I binding receptor families, also increases with aging and AD. These findings suggest the possibility of cell-autonomous MHC-I signaling in regulating microglial reactivation and neurodegeneration.
Article
Geriatrics & Gerontology
Ramasamy Selvarani, Hoang Van Michelle Nguyen, Nidheesh Thadathil, Roman F. Wolf, Willard M. Freeman, Christopher D. Wiley, Sathyaseelan S. Deepa, Arlan Richardson
Summary: This study utilized knockin mouse models to investigate the impact of necroptosis-induced chronic inflammation on aging and age-related diseases. The findings revealed a significant association between increased necroptosis, inflammation, and various age-related pathological changes.
Meeting Abstract
Ophthalmology
Ana J. Chucair-Elliott, Sarah Ocanas, Kevin Pham, Michael Van der Veldt, Ashley Cheyney, David Stanford, Michael H. Elliott, Willard Freeman
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)