Despite the critical impact of glaucoma on global blindness, its aetiology is not fully characterised. Elevated intraocular pressure is highly associated with glaucomatous optic neuropathy. However, visual field loss still progresses in some patients with normal or even low intraocular pressure. Vascular factors have been suggested to play a role in glaucoma development, based on numerous studies showing associations of glaucoma with blood pressure, ocular perfusion pressure, vasospasm, cardiovascular disease and ocular blood flow. As the retinal vasculature is the only part of the human circulation that readily allows non-invasive visualisation of the microcirculation, a number of quantitative retinal vascular parameters measured from retinal photographs using computer software (eg, calibre, fractal dimension, tortuosity and branching angle) are currently being explored for any association with glaucoma and its progression. Several population-based and clinical studies have reported that changes in retinal vasculature (eg, retinal arteriolar narrowing and decreased fractal dimension) are associated with optic nerve damage and glaucoma, supporting the vascular theory of glaucoma pathogenesis. This review summarises recent findings on the relationships between quantitatively measured structural retinal vascular changes with glaucoma and other markers of optic nerve head damage, including retinal nerve fibre layer thickness. Clinical implications, recent new advances in retinal vascular imaging (eg, optical coherence tomography angiography) and future research directions are also discussed.
Adrenomedullin (ADM) is a potent vasorelaxant peptide that plays important roles in cardiovascular homeostasis and inflammatory response. ADM derived from macrophages is one of the major sources of ADM that is produced in the inflammatory process. To assess the functions of ADM in inflammation, we studied the temporal changes in ADM production and its effect on secretion of macrophage migration inhibitory factor (MIF) and cytokine response of NR8383 rat macrophages activated by lipopolysaccharide (LPS). NR8383 cells were stimulated by LPS in the absence and presence of exogenous ADM, and the concentrations of ADM, MIF, and proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta) in the culture media and gene expressions of the cells were measured. We confirmed that the secretion and mRNA expression of ADM in the macrophages were markedly increased by LPS. ADM increased initial secretion of MIF and IL-1beta from both nonstimulated and LPS-stimulated cells, and it also increased basal and LPS-induced IL-6 secretion of the cells by 2- to 15-fold. However, it reduced secretion of TNF-alpha from LPS-stimulated cells by 34-56%. Our results suggest that ADM modulates MIF secretion and cytokine production and plays important roles in both the initiation and propagation of the inflammatory response.
Proenkephalin mRNA has been detected in striatum, hypothalamus, cortex, cerebellum, hippocampus, midbrain, and brain stem of rat by RNA ("Northern") blot analysis using a 918-base-pair DNA hybridization probe complementary to proenkephalin mRNA [Comb, M., Enkephalins have been proposed to function as putative neurotransmitters or neuromodulators in brain. Although their distribution and location in various brain structures is known (1, 2), there is no way to determine their rate of utilization. Hence, the changes in enkephalin content of selected brain structures that are elicited by drug treatment cannot be easily interpreted in terms of inhibition or increase of rates of enkephalin utilization. One reason for such difficulty is lack of understanding of the enzymatic processes that regulate the formation of various molecular forms of enkephalins from proenkephalin, the high molecular weight precursor of enkephalin that contains one or more replicas of at least four molecular forms of enkephalin peptides [referred to as proenkephalin A by Kakidani et al. (3)]. The successful cloning and sequence analysis of the mRNA for proenkephalin from bovine adrenal medulla (4,5) and human pheochromocytoma (6) provide a method to determine whether an increase in the content of a given enkephalin in a brain structure is associated with an increase in the amount of the specific mRNA for proenkephalin. We have reasoned that, when an increase in enkephalin content is associated with an increase in proenkephalin mRNA content, one could infer that the increase in enkephalin content might reflect an increase in availability of the peptide.We report the use of the cDNA probe for human pheochromocytoma proenkephalin (6) to determine whether repeated daily injections of haloperidol in doses that cause a selective increase of striatal enkephalin content (7) also cause a selective increase in proenkephalin mRNA content in striatum. In a previous paper, indirect evidence was presented suggesting that repeated daily injection of haloperidol increases enkephalin biosynthesis in striatum (8): we now report that haloperidol increases proenkephalin mRNA in striatum but not in other brain areas in which the enkephalin content fails to in--crease. MATERIALS AND METHODSTreatment of Animals. Sprague-Dawley male rats (Zivic Miller, Allison Park, PA) weighing 200-300 g were maintained at constant temperature (23-250C), six per cage, in a room illuminated with alternating light and dark cycles (14 and 10 hr, respectively). Haloperidol (McNeil Pharmaceutical, Spring House, PA) was dissolved in a few drops of glacial acetic acid, and the solution was adjusted to pH 6 with 10 N NaOH and diluted with saline. Animals were injected intraperitoneally with 1 to 2 mg/kg of body weight daily for 2 to 3 wk and sacrificed 24 hr after the last injection. The animals were decapitated and the brain regions were dissected according to the method of Glowinski and Iverson (9). Tissues were immediately frozen and stored in liquid nitrogen for analysis at a ...
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