Contribution of Nitric Oxide-Producing Cells in Normal and Diabetic Rat Retina

Goto, Ryotaro; Doi, Motoaki; Ma, Ning; Semba, Reiji; Uji, Yukitaka

doi:10.1007/s10384-004-0213-5

Cited by 21 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This parallels results in the retina during the early stages of STZ-induced diabetes 32 and underscores the contribution of nitric oxide to the pathogeneses of retinopathy in obese animals, as previously demonstrated in diabetic retinopathy in STZ rat retinas. 33 Notably, pericyte loss has also been described as an early pathological feature of diabetic retinopathy. 34 In close contact with retinal capillaries, these cells are important for the tightness of the inner blood-retina barrier 35 and for the integrity of the endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

et al. 2010

View full text Add to dashboard Cite

Retinopathy has been increasing in prevalence as a consequence of type 2 diabetes and a cluster of coexisting risk factors characterized as the metabolic syndrome. However, the combined effects of these conditions on the retina are poorly understood. Therefore, we focused on the spontaneously hypertensive corpulent rat (SHR/N-cp), a model with type 2 diabetes, obesity and features of the metabolic syndrome to characterize retinal changes at a structural and functional level. SHR/N-cp males at 4 and 8 months of age were used in this study. Metabolic parameters and blood pressure were measured by standard methods. Morphology was investigated by histological techniques supplemented by nicotinamide adenine dinucleotide phosphate-diaphorase staining of whole mounts and fluorescein angiography to analyze the retinal vasculature. The in vivo function of the retina was examined by electroretinography (ERG). Obese SHR/N-cp rats were hypertensive and showed significant increases in body weight, serum levels of glucose, triglycerides, total cholesterol and urinary glucose excretion compared with lean controls (Po0.01 for each). Histology indicated an overall intact integrity of the retina and aspects of microangiopathy in obese SHR/N-cp rats. ERG revealed intact processing of light signals but significantly decreased amplitudes of b-waves for all (Po0.01) and of a-waves for some examined light intensities (Po0.05). Oscillatory potentials were significantly protracted (Po0.01), whereas amplitudes were not reduced. Microangiopathy and electroretinographic deficits combine to produce an early non-proliferative retinopathy phenotype in the obese SHR/N-cp rats. Thus, this model represents a valuable experimental tool to obtain further insights into the mechanisms of retinopathy in the context of obesity, type 2 diabetes and metabolic syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

et al. 2010

View full text Add to dashboard Cite

show abstract

“…[202][203][204][205][206] As early as one to three weeks after STZ-induction, fewer eNOSand nNOS-positive cells were found in diabetic rat retina compared with control retina. 201,207 Abu El-Asrar et al 205 found elevated iNOS immunoreactivity in Müller cells in human diabetic retina. Müller cells span almost the entire width of the retina and are important for neuronal support.…”

Section: Nitric Oxidementioning

confidence: 99%

“…Hyperglycaemia increases iNOS activity, leading to excess nitric oxide, which is thought to contribute to diabetic retinopathy 202–206 . As early as one to three weeks after STZ‐induction, fewer eNOS‐ and nNOS‐positive cells were found in diabetic rat retina compared with control retina 201,207 . Abu El‐Asrar et al 205 found elevated iNOS immunoreactivity in Müller cells in human diabetic retina.…”

Section: Disease Mechanisms Common To Diabetes and Glaucomamentioning

confidence: 99%

Clinical and experimental links between diabetes and glaucoma

Wong

Bui²,

Vingrys³

2011

Clinical and Experimental Optometry

View full text Add to dashboard Cite

Glaucoma is a leading cause of blindness. It is a multifactorial condition, the risk factors for which are increasingly well defined from large-scale epidemiological studies. One risk factor that remains controversial is the presence of diabetes. It has been proposed that diabetic eyes are at greater risk of injury from external stressors, such as elevated intraocular pressure. Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a glaucomatous ganglion cell injury. Several clinical trials have considered whether a link exists between diabetes and glaucoma. In this review, we outline these studies and consider the causes for their lack of concordant findings. We also review the biochemical and cellular similarities between the two conditions. Moreover, we review the available literature that attempts to answer the question of whether the presence of diabetes increases the risk of developing glaucoma. At present, laboratory studies provide robust evidence for an association between diabetes and glaucoma. Key words: diabetes, dyslipidaemia, ganglion cells, glaucoma, hyperglycaemia, intraocular pressure, retina Diabetes is a leading health priority, as it can cause severe systemic complications, such as retinopathy, neuropathy and nephropathy. This metabolic disorder results from either altered secretion of insulin by the pancreas (type 1 diabetes) or insulin resistance at a cellular level (type 2 diabetes). These changes produce widespread abnormalities in glucose uptake, resulting in hyperglycaemia, as well as abnormal metabolism and formation of lipids (Figure 1), which impact on neurons, blood vessels and glial cells. Indeed, this journal carries an excellent review on glial dysfunction in diabetic eyes.1 Many clinicians will be aware of diabetic retinopathy and its classification, as laid out by the National Health and Medical Research Council Guidelines for the Management of Diabetic Retinopathy. 2 The purpose of this review is not to dwell on the specifics of diabetic retinopathy but to consider whether diabetes predisposes the eye to other disorders, in particular glaucoma.Diabetes has been estimated by the World Health Organization to affect more than 180 million people worldwide. Despite increasing awareness and advances in management of this disease, it is anticipated that the number of sufferers of diabetes will rise to over 360 million by 2030.3 Diabetic eye disease is a leading cause of blindness [4][5][6] in those of working age (aged from 30 to 69 years).7 The Wisconsin Epidemiologic Study of Diabetic Retinopathy reports that both the duration of the disease and its type (1 or 2) affect the chance of expressing retinopathy. 8,9 The prevalence of retinopathy after five years (17 to 29 per cent) increases after 15 years to 78 to 100 per cent.Diabetes is known to increase the risk of other health complications, 10 in particular, cardiovascular problems 11-13 and cerebral ischaemia. 14,15 Of particular interest to eye-care practitioners is the question of whether we should adj...

show abstract

“…NAC develop independent from retinal vascularization but their persistence in higher numbers than in the controls shows correlation to the reduced vascular stage of the retina. Retinae with increase of vascular supply like in diabetes show reduced numbers of NAC [11]. Since blood supply is correlated with the activity of the retina, light-dependent changes in NAC [12] might explain their modulating role for both, the neuronal aspects of the retina and the retinal vasculature.…”

Section: Brief Reportmentioning

confidence: 99%

Decreased vascular supply leads to higher numbers of NADPH diaphorase amacrine cells in the degenerating mouse retina

May¹

2017

Histol Cytol Embryol

View full text Add to dashboard Cite

NADPH diaphorase/neuronal nitric oxide synthase stained amacrine cells (NAC) are supposed to interact with the retinal vasculature. To study this hypothesis, the retinae of two different mouse strains and their controls were stained using the NADPH diaphorase technique labelling NAC and vessels. In the retina degeneration (rd) mouse, the total number of NAC in the first weeks during early retinal degeneration was slightly reduced. The number persisted in older animals and did not show the decrease described in normal mice. In the Norrie disease (nd) mouse, early vascular malformation lead to increased numbers of NAC. Although the progress of neural remodelling in the degenerated retina leads to a continuous loss of neurons in general, the NAC persist in higher numbers in parallel with a reduced vascular bed. Brief reportClose association between the retinal vasculature and NADPH diaphorase (NADPH-d)/nNOS stained amacrine cells (NAC) were reported for the rat and primate [1,2] and a regulatory function of these cells on retinal microcirculation discussed. This is supported by physiological findings concerning the intensity of relaxation measured in retinal vessels [3,4].To further study the interdependency between NOS positive amacrine cells and vasculature, two different kinds of retinal degeneration were investigated. One showed degenerative and neovascular processes after normal vascular development (rd mouse [5,6]), the other primary vascular irregularities (nd mouse [7]). Retina whole mounts from rd, nd, and C57BL/6 mice at various ages were stained for NADPH-d as described previously [8]. All animals were kept according to the Declaration of Helsinki and the local rules for animal research.In the rd mouse retina, first NAC somata were detected at P3 in the inner cytoblast layer similar to controls. At P14, the number of NAC was only 80% of that counted in control animals (Table 1). However, this number persisted during ageing resulting in an elevated number of NAC somata at 3 months of age and older (Table 2).First changes of the retinal vasculature were obvious at P14. The outer vascular layer continuously degenerated and was almost completely absent at 6 weeks of age. Sprouting vessels in the retinal pigment epithelium (RPE) layer were noted at four weeks of age, rising in number and size with age. From eight weeks on, RPE cells were found around vessels of the inner vascular layers indicating migration along the vasculature.Combining vascular and NAC alterations in the rd mouse, some relation between both structures can be stated. The first onset of retinal degeneration after P7 [5] lead to decreased numbers of NAC. Vascular degeneration paralleled stabilization of elevated NAC number during further retinal degeneration. Neovascularizations did not alter the increased NAC level.

show abstract

Contribution of Nitric Oxide-Producing Cells in Normal and Diabetic Rat Retina

Abstract: NO might be produced in the GCL and amacrine cells, which show immunoreactivity to L-arginine, L-citrulline, and nNOS. In the early stage of diabetic retinopathy in STZ rat retinas, diabetes disturbed the function of the nNOS-positive amacrine cells and reduced NO production via nNOS.

Cited by 21 publications

References 31 publications

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

Clinical and experimental links between diabetes and glaucoma

Decreased vascular supply leads to higher numbers of NADPH diaphorase amacrine cells in the degenerating mouse retina

Contact Info

Product

Resources

About