Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the major causes of blindness worldwide. The pathogenesis of DR has been investigated using several animal models of diabetes. These models have been generated by pharmacological induction, feeding a galactose diet, and spontaneously by selective inbreeding or genetic modification. Among the available animal models, rodents have been studied most extensively owing to their short generation time and the inherited hyperglycemia and/or obesity that affect certain strains. In particular, mice have proven useful for studying DR and evaluating novel therapies because of their amenability to genetic manipulation. Mouse models suitable for replicating the early, non-proliferative stages of the retinopathy have been characterized, but no animal model has yet been found to demonstrate all of the vascular and neural complications that are associated with the advanced, proliferative stages of DR that occur in humans. In this review, we summarize commonly used animal models of DR, and briefly outline the in vivo imaging techniques used for characterization of DR in these models. Through highlighting the ocular pathological findings, clinical implications, advantages and disadvantages of these models, we provide essential information for planning experimental studies of DR that will lead to new strategies for its prevention and treatment.

The purpose of this study was to determine whether melatonin treatment would mitigate retinal ganglion cell (RGC) death in the developing retina following a hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations, expression of vascular endothelial growth factor receptors, Flt-1 and Flk-1, release of cytochrome c from mitochondria, and caspase-3 expression were examined in the retinas of 1-day-old rats at 3 hr to 14 days after a hypoxic exposure. The mRNA and protein expression of Flt-1 and Flk-1 and the tissue concentration of LPO, TNF-α, and IL-1β were upregulated significantly after the hypoxic exposure, whereas the content of GSH was decreased significantly. RGC cultures also showed increased LPO and decreased GSH levels after hypoxic exposure but these effects were reversed in cells treated with melatonin. TNF-α and IL-1β expression was specifically located on microglial cells, whereas Flt-1 and Flk-1 was limited to RGCs as confirmed by double immunofluorescence labeling. Cultures of hypoxic microglial cells treated with melatonin showed a significant reduction in the release of these cytokines as compared to untreated hypoxic cells. Hypoxia induced increase in the cytosolic cytochrome c and caspase-3 in RGCs was attenuated with melatonin treatment. The results suggest that, in hypoxic injuries, melatonin is neuroprotective to RGCs in the developing retina through its antioxidative, anti-inflammatory, and anti-apoptotic effects. Melatonin suppressed Flt-1 and Flk-1 expression in retinal blood vessels, which may result in reduced retinal vascular permeability and it also preserved mitochondrial function as shown by a reduction in cytochrome c leakage into the cytosol. The results may have therapeutic implications for the management of retinopathy of prematurity.

No abstract

Cell's behaviours of like growth, motility, differentiation and apoptosis are regulated by signals received from their environment. These extracellular signaling molecules include neurotransmitters, hormones and growth factors which regulate the activation of intracellular signaling pathways leading to changes in gene expression and cell fate. Cholinergic system through muscarinic M1 and M3 receptors play an important role in the regulation of pancreatic b-cell proliferation and insulin secretion. Cholinergic activity was decreased in the brain regions-hypothalamus, brain stem, corpus striatum, cerebral cortex and cerebellum during pancreatic regeneration. Muscarinic M1 receptors were decreased at time of regeneration while M3 receptors showed an increase. Gene expression studies confirmed the mRNA level of M1 and M3 receptors. These changes in the muscarinic receptors regulate sympathetic activity and maintain glucose level. Pancreatic muscarinic M1 and M3 receptor activity were increased during proliferation indicating that both receptors are stimulatory to pancreatic b-cell division. Acetylcholine dose dependently increased EGF induced DNA synthesis in pancreatic islets in vitro which is inhibited by muscarinic antagonist atropine confirming the role of muscarinic receptors. Acetylcholine also stimulated glucose induced insulin secretion in vitro which is inhibited by muscarinic M1 and M3 receptor antagonists. Thus it is suggested that central muscarinic M1 and M3 receptor subtypes functional difference regulates sympathetic and parasym-pathetic systems which control the islet cell proliferation and glucose homeostasis. Hydroxymethylglutaryl-coenzyme reductase inhibitors (statins) are widely used clinically to reduce serum low density lipoprotein but little is known about their effects in the central nervous system. Sprague-Dawley rats were administered simvastatin or pravastatin (10 mg, p.o.) once daily for 4 weeks. Serum triglyceride levels were similarly reduced in the simvastatin-treated (45%) and pravastatin-treated (48%) groups. Serum cholesterol levels, however, remained unchanged in both groups. Simvastatin treatment increased the expression of eNOS, D1 and D2 receptors at both mRNA (2.1-fold, 1.6-fold and 2.2-fold, respectively) and protein (1.8-fold, 1.3-fold and 1.5-fold, respectively) levels in the frontal cortex, but not in the striatum. Similar changes were not observed in the frontal cortex of the pravastatin-treated rats. There were also no observable changes in the expression of nNOS and iNOS in simvastatin-treated rats. These results suggest that lipophilic statins can alter dopaminergic functions via a central mechanism. Thus, their use may have important implications in the brain reward and reinforcing circuits as well as in disease states associated with dopaminergic abnormality. It is tempting to suggest that the up-regulation eNOS and the two dopamine receptors may be linked in a cause-effect relationship after simvastatin treatment. Prostaglandin E 2 (PGE 2) is a well established hyper...