Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization

AbstractRetinal levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, were measured and correlated with the ischemia-induced retinal neovascularization in rats. The retinas with neovascularization showed a 5-fold increase in VEGF while 2-fold decrease in PEDF, compared to the age-matched controls, resulting in an increased VEGF/PEDF ratio. The time course of the VEGF/PEDF ratio change correlated with the progression of retinal neovascularization. Changes in the VEGF and PEDF mRNAs preceded their protein level changes. These results suggest that an unbalance between angiogenic stimulators and inhibitors may contribute to retinal neovascularization

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Stresses encountered during human islet isolation lead to unavoidable beta-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, beta-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less beta-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Farmers’ attitudes about farming and the environment: A survey of conventional and organic farmers

Farmers have been characterized as people whose ties to the land have given them a deep awareness of natural cycles, appreciation for natural beauty and sense of responsibility as stewards. At the same time, their relationship to the land has been characterized as more utilitarian than that of others who are less directly dependent on its bounty. This paper explores this tension by comparing the attitudes and beliefs of a group of conventional farmers to those of a group of organic farmers. It was found that while both groups reject the idea that a farmer’s role is to conquer nature, organic farmers were significantly more supportive of the notion that humans should live in harmony with nature. Organic farmers also reported a greater awareness of and appreciation for nature in their relationship with the land. Both groups view independence as a main benefit of farming and a lack of financial reward as its main drawback. Overall, conventional farmers report more stress in their lives although they also view themselves in a caretaker role for the land more than do the organic farmers. In contrast, organic farmers report more satisfaction with their lives, a greater concern for living ethically, and a stronger perception of community. Finally, both groups are willing to have their rights limited (organic farmers somewhat more so) but they do not trust the government to do so.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83671/1/Sullivan,_S.,_E._McCann,_R._De_Young_&_D._Erickson_(1996)._Farmers_attitudes_about_farming_and_the_environment,_JAEE,_9,_123-143.pd

Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

PURPOSE. The current study examined if opioid-receptoractivation by morphine can improve retinal function and retinal ganglion cell (RGC) integrity in a chronic glaucoma rat model. METHODS. IOP was raised in Brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated daily with 1 mg/kg morphine for 28 days at 24-hour intervals; animals were examined for changes in IOP by a TonoLab tonometer. Pattern-ERG (PERG) was obtained in response to contrast-reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Changes in the expression pattern of TNF-a and caspases were measured by Western blotting. RESULTS. A significant IOP elevation was seen as early as 7 days, and maintained for up to 8 weeks, after surgery. PERG amplitudes were significantly reduced in ocular-hypertensive eyes (15.84 6 0.74 lvolts) when compared with normal eyes (19 6 0.86 lvolts). PERG deficits in hypertensive eyes were reversed by morphine treatment (18.23 6 0.78 lvolts; P < 0.05). In untreated rats, a 24% reduction in labeled RGCs was measured in the hypertensive eye compared with the normal eye. This reduction in RGC labeling was significantly ameliorated in the presence of morphine. In retinal samples, TNF-a, caspase-8, and caspase-3 expressions were significantly upregulated in ocular hypertensive eyes, but completely inhibited in the morphine-treated animals. CONCLUSIONS. These data provide evidence that activation of opioid receptors can provide significant improvement in PERG and RGC integrity against glaucomatous injury. Mechanistic data provide clues that activation of one or more opioid receptors can reduce glaucomatous-injury via suppression of TNF-a and caspase activation. (Invest Ophthalmol Vis Sci

Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury

Citation: Fan J, Wu BX, Crosson CE. Suppression of acid sphingomyelinase protects the retina from ischemic injury. Invest Ophthalmol Vis Sci. 2016;57:4476-4484. DOI:10.1167/ iovs.16-19717 PURPOSE. Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. However, the role ASMase plays in ischemic retinal injury has not been investigated. The purpose of this study was to investigate how reduced ASMase expression impacts retinal ischemic injury. METHODS. Changes in ceramide levels and ASMase activity were determined by high performance liquid chromatography-tandem mass spectrometry analysis and ASMase activity. Retinal function and morphology were assessed by electroretinography (ERG) and morphometric analyses. Levels of TNF-a were determined by ELISA. Activation of p38 MAP kinase was assessed by Western blot analysis. RESULTS. In wild-type mice, ischemia produced a significant increase in retinal ASMase activity and ceramide levels. These increases were associated with functional deficits as measured by ERG analysis and significant structural degeneration in most retinal layers. In ASMase þ/À mice, retinal ischemia did not significantly alter ASMase activity, and the rise in ceramide levels were significantly reduced compared to levels in retinas from wild-type mice. In ASMase þ/À mice, functional and morphometric analyses of ischemic eyes revealed significantly less retinal degeneration than in injured retinas from wild-type mice. The ischemia-induced increase in retinal TNF-a levels was suppressed by the administration of the ASMase inhibitor desipramine, or by reducing ASMase expression. CONCLUSIONS. Our results demonstrate that reducing ASMase expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators plays a role in the development of ischemic retinal injury. Modulating ASMase may present new opportunities for adjunctive therapies when treating retinal ischemic disorders