A5047873646- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Advanced Glycation End Products research
- Barrier Structure and Function Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Connexins and lens biology
- Retinal Imaging and Analysis
- Neuroscience and Neuropharmacology Research
- Glaucoma and retinal disorders
- Retinopathy of Prematurity Studies
- Photoreceptor and optogenetics research
- Pancreatic function and diabetes
- Neurological Disorders and Treatments
- Neurological Disease Mechanisms and Treatments
- Retinal and Optic Conditions
- Extracellular vesicles in disease
- Receptor Mechanisms and Signaling
- Connective tissue disorders research
- Genomics, phytochemicals, and oxidative stress
- Retinoids in leukemia and cellular processes
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Biochemical effects in animals
- Retinal and Macular Surgery
- Cellular transport and secretion
Penn State Milton S. Hershey Medical Center
2015-2024
Pennsylvania State University
2008-2024
Hershey (United States)
2018
Ophthalmology Associates (United States)
2000-2010
University College London
2010
Breakthrough T1D
2008
Columbia University
2003
Geisinger Health System
1998-1999
University of Saskatchewan
1994-1997
The Open University
1989-1991
This study determined whether retinal degeneration during diabetes includes neural cell apoptosis. Image analysis of sections from streptozotocin (STZ) diabetic rats after 7.5 months STZ identified 22% and 14% reductions in the thickness inner plexiform nuclear layers, respectively (P < 0. 001). The number surviving ganglion cells was also reduced by 10% compared to controls 0.001). In situ end labeling DNA terminal dUTP nick (TUNEL) a 10-fold increase frequency apoptosis whole-mounted rat...
Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches understand pathophysiology improve detection, prevention, retinopathy. This perspective considers how unique anatomy physiology may predispose it metabolic stresses diabetes. roles neural retinal alterations impaired insulin action in pathogenesis...
Vascular endothelial growth factor (VEGF) may have a physiologic role in regulating vessel permeability and contributes to the pathophysiology of diabetic retinopathy as well tumor development. We set out ascertain mechanism by which VEGF regulates paracellular rats. Intra-ocular injection caused post-translational modification occludin determined gel shift from 60 62 kDa. This event began 15 min post-injection was maximal 45 min. Alkaline phosphatase treatment revealed this change...
Blood-retinal barrier (BRB) breakdown is a hallmark of diabetic retinopathy, but the molecular changes that cause this pathology are unclear. Occludin transmembrane component interendothelial tight junctions may regulate permeability at BRB. In study, we examined effects vascular endothelial growth factor (VEGF) and diabetes on occludin content function. Sprague-Dawley rats were made by intravenous streptozotocin injection, age-matched animals served as controls. After 3 months, BRB was...
This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The mutation results a single amino acid substitution insulin 2 gene that causes misfolding protein. arose and is maintained on C57BL/6J background. Male mice heterozygous for this have progressive loss beta-cell function, decreased pancreatic density, significant hyperglycemia, early 4 weeks age.Heterozygous were bred to mice, male offspring monitored beginning at 4.5 age. After 36 retinas...
The early pathophysiology of diabetic retinopathy and the involvement neural vascular malfunction are poorly understood. Glial cells provide structural metabolic support for retinal neurons blood vessels, become reactive in certain injury states. We therefore used streptozotocin rat model short-term to study glial reactivity other functions retina first months after onset diabetes. With a two-site enzyme-linked immunosorbent assay, we measured expression intermediate filament fibrillary...
The ability of insulin to protect neurons from apoptosis was examined in differentiated R28 cells, a neural cell line derived the neonatal rat retina. Apoptosis induced by serum deprivation, and number pyknotic cells counted. p53 Akt were immunoblotting after deprivation treatment, caspase-3 activation immunocytochemistry. Serum for 24 h caused ∼20% undergo apoptosis, detected both pyknosis caspase-3. 10 nm maximally reduced amount with similar potency as 1.3 (10 ng/ml) insulin-like growth...
To identify amacrine cells that are vulnerable to degeneration during the early stages of diabetes.Whole retinas from streptozotocin (STZ)-diabetic rats and Ins2(Akita) mice were fixed in paraformaldehyde. Apoptotic retina quantified using terminal dUTP nick-end labeling (TUNEL) active caspase-3 (CM-1) immunohistochemistry. Immunohistochemical markers for choline acetyltransferase (ChAT) tyrosine hyroxylase (TH) also used quantify populations Ins2Akita mouse retinas.The number TUNEL-positive...
To determine the extent of retinal ganglion cell loss and morphologic abnormalities in surviving cells Ins2 Akita/+ diabetic mice.Mice that expressed cyan fluorescent protein (CFP) or yellow (YFP) reporter genes under transcriptional control Thy1 promoter were crossed with mice. After 3 months diabetes, number morphology was analyzed by confocal microscopy. The CFP-positive quantified retinas Ins2(Akita/+) Thy1-CFP examined, dendritic density Thy1-YFP mice using Sholl analysis.Thy1-CFP...
Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative anti-inflammatory and neuroprotective properties, to prevent permeability inflammation following ischemia-reperfusion (IR) injury, model neurodegeneration breakdown blood-retinal barrier (BRB). Male Sprague–Dawley rats were subjected 45 min pressure-induced ischemia, contralateral eye serving as control. Rats treated Mino...
Purpose: Current evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy. Our main goal was to examine whether, human retina, common proteins and pathways are shared with brain neurodegenerative diseases. Methods: A proteomic analysis performed on three groups postmortem retinas matched by age: nondiabetic control (n = 5), without glial activation 5). Retinal lysates from each group were pooled run SDS-PAGE gel. Bands analyzed...
The blood-brain barrier (BBB) is an essential feature of the microvasculature in neural tissues. Agrin, a synapse organizing molecule at neuromuscular junction, also accumulates on brain and may be involved BBB formation function. We investigated developmental expression agrin rat chick capillaries by immunohistochemistry immunoblotting. Anti-agrin immunoreactivity (IR) completely ensheathes all observed microvessels labeled with anti-von Willebrand factor adult brains both species. Brain...
Abstract Background Despite advances in the understanding of diabetic retinopathy, nature and time course molecular changes retina with diabetes are incompletely described. This study characterized functional phenotype increasing durations diabetes. Results Using streptozotocin-induced rat model diabetes, levels retinal permeability, caspase activity, gene expression were examined after 1 3 months Gene identified by whole genome microarray confirmed qPCR same set animals as used analyses...
Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested hypothesis that diabetes decreases retinal expression presynaptic proteins involved synaptic function. The protein mRNA contents for synapsin I, synaptophysin, vesicle-associated membrane 2, synaptosomal-associated 25 kDa postsynaptic density 95 were measured by immunohistochemistry, immunoblotting real-time quantitative polymerase chain reaction whole retinas...