Publications by authors named "Maria B Grant"

Glucose-sensing ChREBP and MondoA are transcriptional factors involved in lipogenic, inflammatory, and insulin signaling pathways implicated in metabolic disorders; however, limited ocular studies have been conducted on these proteins. We aimed to investigate the potential role of ChREBP in pathogenesis of diabetic retinopathy (DR). We used diabetic human and mouse retinal cryosections analyzed by immunohistochemistry.

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Cholesterol crystals (CC) can be responsible for a range of clinical syndromes in the retina from asymptomatic plaques to retinal artery occlusion with clinical trials providing evidence for the efficacy in lipid lowering therapies in preventing ocular pathology. Much of the literature has focused on CC in retinal circulation as a marker of poor systemic health and have attempted to use them to categorize risk of mortality and stroke. More recently cholesterol accumulation and CC formation have been linked to development of diabetic retinopathy with CC formation in the retina due to aberrant retinal cholesterol homeostasis and not simply systemic dyslipidemia.

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Article Synopsis
  • The study utilized VESgen software to analyze vascular changes in eyes of patients with varying degrees of diabetic retinopathy (DR), comparing data from fluorescein angiography (FA) and optical coherence tomography angiography (OCTA).
  • Two cohorts were examined: the first included type 2 diabetes (T2D) patients with mild non-proliferative DR and nondiabetic controls, while the second focused on T2D patients and controls imaged using OCTA.
  • Results showed that FA provided better insights into the structure of small microvessels, while OCTA was more effective at assessing vessel density, highlighting the potential for VESgen to improve our understanding of early
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Article Synopsis
  • The text discusses how non-invasive and affordable eye imaging techniques can enhance the detection and monitoring of systemic diseases, particularly cardiovascular issues.
  • A workshop held by the National Heart, Lung, and Blood Institute in October 2022 outlined research opportunities and knowledge gaps related to retinal biomarkers and their connection to cardiovascular diseases.
  • Notable gaps include improving image capture methods, standardizing techniques for healthcare workers, integrating advanced imaging with lifestyle and health data, and leveraging AI to enhance risk identification in diverse populations.
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Background: Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels.

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 Beginning January 26, 2022, the U.S. Medical Licensing Exam (USMLE) Step 1 changed from a numerical score to pass/fail (P/F).

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The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 months following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes.

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Previously, the RXR agonist UAB126 demonstrated therapeutic potential to treat obese mice by controlling blood glucose levels (BGL) and altering the expression of genes associated with lipid metabolism and inflammatory response. The purpose of the study was to assess the effects of UAB126 on the progression of diabetic retinopathy (DR) in rodent models of type 1 diabetes (T1D), streptozotocin-induced, and type 2 diabetes (T2D), in db/db mice. UAB126 treatment was delivered either by oral gavage for 6 weeks or by topical application of eye drops for 2 weeks.

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Previously, the RXR agonist UAB126 demonstrated therapeutic potential to treat obese mice by controlling blood glucose levels (BGL) and altering the expression of genes associated with lipid metabolism and inflammatory response. The purpose of the study was to assess UAB126 effect in progression of diabetic retinopathy (DR) in rodent models of Type1 diabetes (T1D), streptozotocin-induced, and Type2 diabetes (T2D), the db/db mice. UAB126 treatment was delivered either by oral gavage for 6 weeks or by topical application of eye drops for 2 weeks.

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Aims/hypothesis: Hyper-reflective crystalline deposits found in retinal lesions have been suggested to predict the progression of diabetic retinopathy, but the nature of these structures remains unknown.

Methods: Scanning electron microscopy and immunohistochemistry were used to identify cholesterol crystals (CCs) in human donor, pig and mouse tissue. The effects of CCs were analysed in bovine retinal endothelial cells in vitro and in db/db mice in vivo using quantitative RT-PCR, bulk RNA sequencing, and cell death and permeability assays.

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Article Synopsis
  • Tyrosine kinase inhibitors (TKIs) are good at treating chronic myelogenous leukemia (CML), but some stubborn leukemia stem cells stay around and need to be eliminated for a cure.
  • In experiments with mice, scientists discovered that while TKIs impacted the energy processes in CML cells, over time, some cells adapted and survived.
  • By blocking a protein called HIF-1, researchers found that they could kill off these unwanted leukemia stem cells, suggesting a new way to boost the effectiveness of TKI treatment.
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Purpose: The expression of silent information regulator (SIRT) 1 is reduced in diabetic retinopathy (DR). Previous studies showed that alterations in SIRT1 messenger RNA (mRNA) and protein expression are implicated in progressive inflammation and formation of retinal acellular capillaries. Treatment with the SIRT1 agonist, SRT1720, improved visual response by restoration of a- and b-wave responses on electroretinogram scotopic measurements in diabetic (db/db) mice.

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We reported previously that β-site amyloid precursor protein cleaving enzyme (BACE1) is strongly expressed in the normal retina and that BACE1 mice develop pathological phenotypes associated with age-related macular degeneration (AMD). BACE1 expression is increased within the neural retina and retinal pigment epithelium (RPE) in AMD donor eyes suggesting that increased BACE1 is compensatory. We observed that AAV-mediated BACE1 overexpression in the RPE was maintained up to 6 months after AAV1-BACE1 administration.

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This study investigated retinal changes in a Western diet (WD)-induced nonhuman primate model of type 2 diabetes. Rhesus nonhuman primates, aged 15 to 17 years, were fed a high-fat diet (n = 7) for >5 years reflective of the traditional WD. Age-matched controls (n = 6) were fed a standard laboratory primate diet.

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Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating megakaryocytes in a large cohort of inpatients with COVID-19 and correlated the subpopulation frequencies with clinical outcomes. Using peripheral blood, we show that megakaryocytes are increased in the systemic circulation in COVID-19, and we identify and validate S100A8/A9 as a defining marker of megakaryocyte dysfunction.

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Intestinal lymphatic, known as lacteal, plays a critical role in maintaining intestinal homeostasis by regulating several key functions, including the absorption of dietary lipids, immune cell trafficking, and interstitial fluid balance in the gut. The absorption of dietary lipids relies on lacteal integrity, mediated by button-like and zipper-like junctions. Although the intestinal lymphatic system is well studied in many diseases, including obesity, the contribution of lacteals to the gut-retinal axis in type 1 diabetes (T1D) has not been examined.

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(1) Background: Retinal vascular imaging plays an essential role in diagnosing and managing chronic diseases such as diabetic retinopathy, sickle cell retinopathy, and systemic hypertension. Previously, we have shown that individuals with pulmonary arterial hypertension (PAH), a rare disorder, exhibit unique retinal vascular changes as seen using fluorescein angiography (FA) and that these changes correlate with PAH severity. This study aimed to determine if color fundus (CF) imaging could garner identical retinal information as previously seen using FA images in individuals with PAH.

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Background: We examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D).

Methods: T1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II); mice were orally administered a (LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention. mice with genetic overexpression of by small intestine epithelial cells () were similarly examined.

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Vascular stiffness is an independent predictor of human vascular diseases and is linked to ischemia, diabetes, high blood pressure, hyperlipidemia, and/or aging. Blood vessel stiffening increases owing to changes in the microscale architecture and/or content of extracellular, cytoskeletal, and nuclear matrix proteins. These alterations, while best appreciated in large blood vessels, also gradually occur in the microvasculature and play an important role in the initiation and progression of numerous microangiopathies including diabetic retinopathy.

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Hematopoietic cells play a crucial role in the adult retina in health and disease. Monocytes, macrophages, microglia and myeloid angiogenic cells (MACs) have all been implicated in retinal pathology. However, the role that hematopoietic cells play in retinal development is understudied.

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Age-related macular degeneration (AMD) is a complex disease with increasing numbers of individuals being afflicted and treatment modalities limited. There are strong interactions between diet, age, the metabolome, and gut microbiota, and all of these have roles in the pathogenesis of AMD. Communication axes exist between the gut microbiota and the eye, therefore, knowing how the microbiota influences the host metabolism during aging could guide a better understanding of AMD pathogenesis.

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Article Synopsis
  • The study investigates how COVID-19 affects gut health, noting that around 50% of COVID-19 patients experience gastrointestinal issues.
  • Researchers analyzed plasma samples from 146 COVID-19 patients and 47 healthy individuals, finding notable differences in gut microbiome composition and gut permeability markers.
  • The results suggest that gut dysbiosis and increased gut permeability in COVID-19 patients could lead to worse outcomes, indicating potential for therapies targeting gut health to improve patient recovery.
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Pulmonary arterial hypertension (PAH) is classically considered an isolated small vessel vasculopathy of the lungs with peripheral pulmonary vascular obliteration. Systemic manifestations of PAH are increasingly acknowledged, but data remain limited. We hypothesized that retinal vascular changes occur in PAH.

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