Sayon Roy

Sayon Roy
Boston University | BU · Department of Medicine, Section of Endocrinology, Diabetes & Nutrition, and Department of Ophthalmology

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102
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Publications (102)
Article
Full-text available
Lysyl oxidases are multifunctional proteins derived from five lysyl oxidase paralogues (LOX) and lysyl oxidase-like 1 through lysyl oxidase-like 4 (LOXL1–LOXL4). All participate in the biosynthesis of and maturation of connective tissues by catalyzing the oxidative deamination of lysine residues in collagens and elastin, which ultimately results in...
Article
Full-text available
Diabetic retinopathy (DR) is one of the most common causes of vision loss and blindness among the working-age population. High glucose (HG)-induced decrease in mitochondrial connexin 43 (mtCx43) level is known to promote mitochondrial fragmentation, cytochrome c release, and apoptosis in retinal endothelial cells associated with DR. In this study,...
Article
Full-text available
High glucose (HG)-induced Drp1 overexpression contributes to mitochondrial dysfunction and promotes apoptosis in retinal endothelial cells. However, it is unknown whether inhibiting Drp1 overexpression protects against the development of retinal vascular cell loss in diabetes. To investigate whether reduced Drp1 level is protective against diabetes...
Article
Full-text available
This study investigates whether reduced optic atrophy 1 (Opa1) level promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy (DR). Four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Opa1+/− mice, and diabetic Opa1+/− mice were used in this study. 16 weeks after diabetes onset,...
Chapter
Diabetic retinopathy (DR) is one of the most common forms of microvascular complications of diabetes. Unfortunately, there is no cure for this debilitating ocular complication that holds particular significance due to its detrimental effects on vision, which ultimately leads to vision loss and blindness. Hyperglycemia, the most prominent characteri...
Article
Full-text available
Changes in retinal microcirculation are associated with the development of diabetic retinopathy (DR). However, it is unclear whether such changes also develop in capillary beds of other non-retinal tissues. Here, we investigated microcirculatory changes involving velocity of rolling neutrophils, adherence of neutrophils, and leukostasis during deve...
Article
Full-text available
To investigate whether high glucose (HG) alters Rab20 expression and compromises gap junction intercellular communication (GJIC) and cell survival, retinal cells were studied for altered intracellular trafficking of connexin 43 (Cx43). Retinal endothelial cells (RRECs) and retinal Müller cells (rMCs) were grown in normal (N; 5 mM glucose) or HG (30...
Article
Vascular basement membrane (BM) thickening has been hailed over half a century as the most prominent histological lesion in diabetic microangiopathy, and represents an early ultrastructural change in diabetic retinopathy (DR). Although vascular complications of DR have been clinically well established, specific cellular and molecular mechanisms und...
Article
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Purpose: To determine whether high glucose (HG) or diabetes alters mitochondrial morphology and promotes mitochondrial fragmentation in retinal vascular cells and thereby triggers apoptosis associated with diabetic retinopathy. Methods: To assess whether diabetes promotes mitochondrial fragmentation and thereby triggers apoptosis, retinas from n...
Article
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Diabetic retinopathy is a prevalent microvascular complication characterized by apoptotic vascular cell loss in the retina. Previous studies have shown that high glucose (HG)-induced mitochondrial fragmentation plays a critical role in promoting retinal vascular cell apoptosis. Here, we investigated whether downregulation of mitochondrial fission g...
Article
Full-text available
Purpose: To determine whether high glucose (HG) compromises internalization of lysyl oxidase (LOX) through excess binding of LOX with extracellular matrix (ECM) proteins. Methods: To determine whether HG promotes binding of LOX with ECM proteins, fibronectin (FN) and collagen IV (Coll IV), total or ECM-only proteins from rat retinal endothelial...
Article
Full-text available
Animal studies have shown diabetes-induced lysyl oxidase (LOX) upregulation promotes blood-retinal-barrier breakdown and retinal vascular cell loss associated with diabetic retinopathy (DR). However, it is unclear whether changes in LOX expression contribute to the development and progression of DR. To determine if vitreous LOX levels are altered i...
Article
Diabetic retinopathy (DR) is characterized by apoptotic cell loss in the retinal vasculature. Lysyl oxidase propeptide (LOX-PP), released during LOX processing, has been implicated in promoting apoptosis in various diseased tissues. However, its role in the development and progression of DR is unknown. We investigated whether high glucose (HG) or d...
Article
Retinal capillary basement membrane (BM) thickening is closely associated with the development of vascular lesions in diabetic retinopathy. Thickened capillary BM can compromise blood-retinal-barrier characteristics and contribute to retinal vascular permeability, a significant clinical manifestation of diabetic retinopathy. We have previously show...
Article
Full-text available
Diabetic bone disease is a complication of type I and type II diabetes, both of which are increasing in the United States and elsewhere. Increased hip and foot fracture rates do not correlate well with changes in bone mineral density, while studies support the importance of collagen structure to bone strength. Extracellular lysyl oxidase (LOX) cata...
Poster
High Glucose Increases Binding of Lysyl Oxidase with Extracellular Matrix Proteins in Retinal Endothelial Cells: Implications for Diabetic Retinopathy
Conference Paper
High Glucose Increases Binding of Lysyl Oxidase with Extracellular Matrix Proteins in Retinal Endothelial Cells: Implications for Diabetic Retinopathy
Article
Full-text available
Purpose: The purpose of this study was to investigate the effect of reducing diabetes-induced lysyl oxidase (LOX) overexpression on vascular cell apoptosis and blood-retinal barrier (BRB) characteristics in diabetic rats. Methods: Nondiabetic rats, diabetic rats, and diabetic rats intravitreally (IV) injected with LOX siRNA or scrambled (scram)...
Article
The aim of this study was to investigate whether inhibition of connexin 43 gap junction-uncoupling is sufficient to prevent retinal vascular cell loss under high glucose condition and reduce cell monolayer permeability. Rat retinal endothelial cells were grown for 3, 5, and 7 days in normal (5 mM) or high glucose (30 mM) medium; in parallel, cells...
Article
In diabetic retinopathy, high glucose (HG)-mediated breakdown in cell-cell communication promotes disruption of retinal homeostasis. Several studies indicate that HG condition alters expression of connexin genes and subsequent gap junction intercellular communication (GJIC) in retinal vascular cells and non-vascular cells. A serious consequence of...
Article
Diabetic retinopathy is the leading cause of blindness in the working age population. Unfortunately, there is no cure for this devastating ocular complication. The early stage of diabetic retinopathy is characterized by the loss of various cell types in the retina, namely endothelial cells and pericytes. As the disease progresses, vascular leakage,...
Article
Full-text available
Purpose To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX...
Article
Full-text available
Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe chan...
Article
Full-text available
Purpose To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR). Methods A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days...
Article
In response to injury, reparative processes are triggered to restore the damaged tissue; however, such processes are not always successful in rebuilding the original state. The formation of fibrous connective tissue is known as fibrosis, a hallmark of the reparative process. For fibrosis to be successful, delicately balanced cellular events involvi...
Article
Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years)...
Article
In the Fenofibric Acid (FA) Intervention and Event Lowering in Diabetes (FIELD) study, FA, a lipid-lowering drug, has been shown to significantly reduce macular edema in diabetic patients. In the present study, we investigated whether FA reduces vascular permeability by inhibiting cyclooxygenase-2 (COX-2), a critical mediator of inflammation, and r...
Article
The vascular basement membrane (BM) contains extracellular matrix (ECM) proteins that assemble in a highly organized manner to form a supportive substratum for cell attachment facilitating myriad functions that are vital to cell survival and overall retinal homeostasis. The BM provides a microenvironment in which bidirectional signaling through int...
Article
The paucity of animal models exhibiting full pathology of diabetic retinopathy (DR) has impeded understanding of the pathogenesis of DR and the development of therapeutic interventions. Here we investigated if hyperhexosemic marmosets (Callithrix jacchus) develop characteristic retinal vascular lesions including macular edema (ME), a leading cause...
Article
Purpose: To investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyte loss. Methods: Retinal Müller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were grown in normal (N) or HG (30 mM glucose)...
Article
Full-text available
Purpose To determine whether downregulation of Connexin 43 (Cx43) expression promotes development of acellular capillaries (ACs), pericyte loss (PL), excess permeability, and retinal thickening in rat retinas. Methods Control rats, diabetic rats, and rats intravitreally injected with Cx43 siRNA or scrambled siRNA were used in this study to determi...
Article
Full-text available
To present our findings in a case of Werner syndrome with refractory cystoid macular edema (CME) and to determine the expression and the distribution of WRN proteins in human retinas. A 35-year-old man with Werner syndrome who developed CME after YAG laser treatment was studied. Optical coherence tomographic (OCT) scans were used to examine the CME...
Article
Purpose: To examine whether c-Fos, phosphorylated c-Jun (p-c-Jun), members of transcriptional factor activator protein 1 (AP-1) family and phosphorylated c-Jun N-terminal kinase (p-JNK) are associated with neuronal degeneration in retinas of diabetic patients. Materials and methods: Retinal cryosections from five pairs of normal and five pairs o...
Article
Purpose: To investigate whether high glucose (HG)-induced downregulation of connexin 43 (Cx43), a gap junction protein, alters ZO-1 and occludin expression and cell monolayer permeability. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM) medium, high glucose (HG; 30 mM) medium, N medium transfected with Cx43 siRNA, o...
Article
Abstract Aim: Altered expression of connexin 43 (Cx43) has been postulated to be involved in the development and progression of various diseases including erectile dysfunction (ED). The aim of this study was to determine whether distribution and density of the gap junction protein Cx43 are altered in human corpus cavernosum (HCC) tissue samples der...
Article
Despite improving standards of care, people with diabetes remain at risk of development and progression of diabetic retinopathy (DR) and visual impairment. Identifying novel therapeutic approaches, preferably targeting more than one pathogenic pathway in DR, and at an earlier stage of disease, is attractive. There is now consistent evidence from tw...
Article
Full-text available
Purpose: To investigate whether high glucose (HG) alters expression of connexin 30.2 (Cx30.2) and influences gap junction intercellular communication (GJIC) in retinal endothelial cells and promotes vascular lesions characteristic of diabetic retinopathy (DR). Methods: Western blot analysis and immunostaining were performed to determine Cx30.2 p...
Article
Full-text available
Background: Use of ultra-high diluted remedies in homeopathy and their claimed efficacy in curing diseases has been challenged time and again by non-believers despite many evidence-based positive results published in favor of their efficacy in curing/ameliorating disease symptoms. Aims: To test the ability of ultra-high diluted homeopathic remedies...
Article
Hyperglycemia, a prominent characteristic of diabetes, has been implicated in the apoptotic death of vascular and neuronal cells in the retina. In diabetic retinopathy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and subsequent breakdown of cellular homeostasis play a critical role in retinal cell death. In particular, changes in...
Article
Full-text available
Purpose To investigate whether high glucose (HG) induces mitochondrial dysfunction and promotes apoptosis in retinal Müller cells. Methods Rat retinal Müller cells (rMC-1) grown in normal (N) or HG (30 mM glucose) medium for 7 days were subjected to MitoTracker Red staining to identify the mitochondrial network. Digital images of mitochondria were...
Article
Purpose To present a case of Werner syndrome accompanied with refractory cystoid macular edema (CME), and analyze the expression and the distribution of WRN proteins in human retinas. Methods A 35-year-old individual with Werner syndrome exhibited CME after YAG laser treatment. Optical coherence tomography (OCT) scans were indicative of CME in the...
Article
Purpose: To determine connexin 43 (Cx43) localization in mitochondria and investigate the effects of high glucose (HG) on mitochondrial Cx43 (mtCx43) expression and whether altered mtCx43 channel activity is involved in promoting apoptosis in retinal endothelial cells. Methods: MtCx43 localization was determined using immunostaining, green fluor...
Article
Full-text available
A sustained gene modulatory strategy is necessary for regulating abnormal gene expression in diabetic retinopathy, a long-term complication. We investigated the efficacy of a small interference RNA (siRNA) strategy in mediating the long-term downregulatory effect of fibronectin (FN) overexpression in vivo. Streptozotocin-induced diabetic rats were...
Article
Mitochondrial dysfunction is known to play a role in retinal vascular cell loss, a prominent lesion of diabetic retinopathy. High glucose (HG) has been reported to induce mitochondrial fragmentation and dysfunction in retinal endothelial cells, contributing to apoptosis. In this study, the effects of HG on mitochondrial morphology, membrane potenti...
Article
The following study was designed to investigate early biosynthetic and ultrastructural changes that alter functional properties of the basement membrane (BM) and affect vascular permeability in diabetic retinopathy. To determine whether altered matrix synthesis affects cell monolayer permeability, rat retinal endothelial cells (RRECs) were grown fo...
Article
To determine whether fenofibric acid (FA) reduces high glucose (HG)-induced basement membrane component overexpression and hyperpermeability in human retinal pigment epithelial (RPE) cells. Retinal pigment epithelial cells (ARPE-19) were cultured for 18 days in normal glucose (5 mM) or HG (25 mM) medium and studied for the effects of FA on fibronec...
Article
Full-text available
In diabetes, retinal vascular basement membrane (BM) undergoes significant thickening and compromises vessel function including increased vascular permeability, a prominent lesion of early diabetic retinopathy. In this study we determined whether altered expression and activity of lysyl oxidase (LOX), a cross-linking enzyme, may compromise vascular...
Article
Vascular basement membrane (BM) thickening is a fundamental structural alteration of small blood vessels in diabetes. Over two decades of research has established hyperglycemia as the primary causal factor mediating this alteration. Various high glucose-induced mechanisms have been investigated and excess synthesis of BM components has been identif...
Article
The goal of this study was to determine whether aging induces retinal vascular lesions that are similar to those seen in diabetic retinopathy. Female rats were randomly divided into four groups; each group represented a time point and consisted of four non-diabetic rats and four diabetic rats. At time points of 3, 12, 18, or 22 months of age, retin...
Article
Full-text available
PURPOSE. To examine whether diabetes-induced connexin 43 downregulation promotes retinal vascular lesions characteristic of diabetic retinopathy (DR). METHODS. Two animal models, streptozotocin-induced diabetic mice and Cx43 heterozygous knockout (Cx43(+/-)) mice, were studied to directly assess whether diabetes reduces the expression of retinal Cx...
Article
Mitochondrial dysfunction has been implicated in diabetic complications; however, it is unknown whether hyperglycemia affects mitochondrial morphology and metabolic capacity during development of diabetic retinopathy. We investigated high glucose (HG) effects on mitochondrial morphology, membrane potential heterogeneity, cellular oxygen consumption...
Article
Full-text available
An early and significant event in diabetic retinopathy is the loss of retinal microvascular pericytes. Studies were performed to investigate pathways through which an advanced glycation endproduct and tumor necrosis factor (TNF)-alpha stimulate apoptosis in retinal pericytes through the activation of the pro-apoptotic transcription factor Forkhead...
Article
Hyperglycemia is the most prevalent characteristic of diabetes and plays a central role in mediating adverse effects on vascular cells during the progression of diabetic vascular complications. In diabetic microangiopathy, hyperglycemia induces biochemical and molecular changes in microvascular cells that ultimately progress to retinal, renal, and...
Article
Full-text available
To investigate early events leading to microvascular cell loss in diabetic retinopathy. FOXO1 was tested in vivo by DNA binding activity and by nuclear translocation in microvascular cells in retinal trypsin digests. In vivo studies were undertaken in STZ-induced diabetic rats and Zucker diabetic fatty rats using the tumor necrosis factor (TNF)-spe...
Article
This study aims to determine whether high glucose-induced inhibition of connexin 43 (Cx43) expression and reduced gap junction intercellular communication (GJIC) promote microvascular endothelial cell loss. To downregulate Cx43 protein expression in rat microvascular endothelial cells (RMECs), the cells were grown in high (30 mM) glucose medium for...
Article
To determine whether tight glycemic control prevents development of basement membrane (BM) thickening in retinal and glomerular capillaries of diabetic rats and whether the extent to which BM thickening develops is linked to fibronectin (FN) overexpression and the degree of hyperglycemia. Retinal and renal cortical tissues obtained from the tightly...
Article
Retinal microvascular cell loss plays a critical role in the pathogenesis of diabetic retinopathy. To examine this further, type 1 streptozotocin-induced diabetic rats and type 2 Zucker diabetic fatty rats were treated by intravitreal injection of the tumor necrosis factor-specific inhibitor pegsunercept, and the impact was measured by analysis of...
Article
Neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. However, the mechanisms for neuronal cell death in diabetic retinopathy remain unclear. To determine whether altered expression of Bax, caspase-9 and -3 is associated with degenerative neurons in diabetic retinopathy. Immunohistochemistry was performed on cryosecti...
Article
Diabetic retinopathy and glaucoma are major diseases that cause blindness in a high percentage of the population. However, the precise mechanisms involved in the onset and the progression of these diseases are still not completely known. Recent studies have shown that there appears to be an association between these two disease processes because th...
Article
The extracellular matrix (ECM) of the trabecular meshwork (TM) is an important determinant of its functional properties. This study was performed to investigate whether overexpression of ECM components, laminin (LM) and collagen type IV (Col) by TM cells may play a role in the development of outflow resistance. To determine the effect of excess LM...
Article
To investigate the effect of chronic hyperglycemia on intraocular pressure (IOP) in patients with diabetes. Cross-sectional study. We prospectively measured the IOP by Goldmann applanation tonometry in patients with diabetes with mild hyperglycemia (glycosylated hemoglobin A1c (HbA1c) < or = 6.5%), moderate hyperglycemia (6.5% < HbA1c < 8.0), and s...
Article
The effect of combined antisense oligonucleotides (AS-oligos) against overexpression of extracellular matrix (ECM) components, fibronectin, laminin, and collagen IV and on cell monolayer permeability was examined in rat microvascular endothelial cells (RMECs) grown in high glucose medium and on retinal vascular permeability in diabetic rats. RMECs...
Article
This study was performed to determine whether early diabetes accelerates retinal neuronal cell death and inhibits neurite regeneration. Five of ten rats were rendered diabetic with streptozotocin injection. After 3 weeks of diabetes, retinas were isolated and retinal explants were cultured in serum-free media. On day 6, the number of neurites was c...
Article
Increased synthesis of extracellular matrix (ECM) contributes to the development of vascular BM thickening, a prominent abnormality in diabetic retinopathy. RNA interference (RNAi) approach was used in this study to examine the effect of small interfering RNAs (siRNAs) for their ability to inhibit ECM-specific gene overexpression under high glucose...