Journal of Ocular Biology, Diseases, and Informatics

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

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Epigenetic modulation of chromatin states constitutes a vital component of the cellular repertoire of transcriptional regulatory mechanisms. The development of new technologies capable of generating genome-wide maps of chromatin modifications has re-energized the field. We are now poised to determine how species- and tissue-specific patterns of DNA methylation, in concert with other chromatin modifications, function to establish and maintain cell- and tissue-specific patterns of gene expression during normal development, cellular differentiation, and disease...

Epigenetic regulation, including DNA methylation, histone modifications, and chromosomal organization, is emerging as a new layer of transcriptional regulation in retinal development and maintenance. Guided by intrinsic transcription factors and extrinsic signaling molecules, epigenetic regulation can activate and/or repress the expression of specific sets of genes, therefore playing an important role in retinal cell fate specification and terminal differentiation during development as well as maintaining cell function and survival in adults...

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Retinal neurons are highly vulnerable to a diverse array of neurotoxic stimuli that leads to their degeneration, which is a major contributor to blindness. This review summarizes the role of epigenetic factors in mediating neuronal homeostasis and survival to protect against cell death and neurodegenerative conditions. Studies in human patients and mouse models implicate numerous chromatin modifications in neuroprotective processes including histone protein acetylation and methylation, DNA methylation, and ATP-dependent nucleosome remodeling...

This chapter reviews the function of microglia and their potential roles in neural inflammation and pathological changes during diabetic retinopathy.

Müller cells, the primary glial cells are a crucial component of the retinal tissue performing a wide range of functions including maintaining the blood-retinal barrier. Several studies suggest that diabetes leads to Müller cell dysfunction and loss. The pathophysiology of hyperglycemia-induced cellular injury of Müller cells remains only poorly understood. Recently, the concept that translocation of the predominantly cytosolic glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to the nucleus and its accumulation in this cellular compartment alters transcriptional events associated with cell death induction has gained major interest...

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The endoplasmic reticulum (ER) is the primary cellular compartment where proteins are synthesized and modified before they can be transported to their destination. Dysfunction of the ER impairs protein homeostasis and leads to the accumulation of misfolded/unfolded proteins in the ER, or ER stress. While it has long been recognized that ER stress is a major cause of conformational disorders, such as Alzheimer's disease, Huntington's disease, certain types of cancer, and type 2 diabetes, recent evidence suggests that ER stress is also implicated in many chronic inflammatory diseases...

The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy...

In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. Adenosine and its receptors have been shown to possess anti-inflammatory properties that have only recently been studied in DR. Here, we review recent studies that determined the roles of adenosine and its associated proteins, including equilibrative nucleoside transporters, adenosine receptors, and underlying signaling pathways in retinal complications associated with diabetes...

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in working-age Americans. DR is traditionally regarded as a disorder of blood-retina barriers, and the leakage of blood content is a major pathological characteristic of the disease. While the breakdown of the endothelial barrier in DR has been investigated extensively, the vascular leakage through the retinal pigment epithelium (RPE) barrier in the disease has not been widely acknowledged. As the blood content leaked through the RPE barrier causes excessive water influx to the retina, the breakdown of the RPE barrier is likely to play a causative role in the development of some forms of diabetic macular edema, a major cause of vision loss in DR...

Neuronal dysfunction has been noted very soon after the induction of diabetes by streptozotocin injection in rats. It is not clear from anatomical evidence whether glial cell dysfunction accompanies the well-documented neuronal deficit. Here, we isolate the Müller cell driven slow-P3 component of the full-field electroretinogram and show that it is attenuated at 4 weeks following the onset of streptozotocin-hyperglycaemia. We also found a concurrent reduction in the sensitivity of the phototransduction cascade, as well as in the components of the electroretinogram known to indicate retinal ganglion cell and amacrine cell integrity...

The pathogenesis of diabetic retinopathy is complex, reflecting the array of systemic and tissue-specific metabolic abnormalities. A range of pathogenic pathways are directly linked to hyperglycaemia and dyslipidaemia, and the retina appears to be exquisitely sensitive to damage. Establishing the biochemical and molecular basis for this pathology remains an important research focus. This review concentrates on the formation of a range of protein adducts that form after exposure to modifying intermediates known to be elevated during diabetes...

Mitochondrial dysfunction is considered to play an important role in the development of diabetic retinopathy. Recent evidence has also shown many similarities between diabetic retinopathy and a low grade chronic inflammatory disease. The aim of this study is to understand the interrelationship between proinflammtory mediator, IL-1β and mitochondrial dysfunction in the accelerated loss of capillary cells in the retina. Using IL-1β receptor gene knockout (IL-1R1(-)/(-)) diabetic mice, we have investigated the effect of regulation of IL-1β on mitochondrial dysfunction and mtDNA damage, and increased retinal capillary cell apoptosis and the development of retinopathy...