retinaldehyde and Diabetic-Retinopathy

The retinal pigment epithelium (RPE) is an specialized epithelium lying in the interface between the neural retina and the choriocapillaris where it forms the outer blood-retinal barrier (BRB). The main functions of the RPE are the following: (1) transport of nutrients, ions, and water, (2) absorption of light and protection against photooxidation, (3) reisomerization of all-trans-retinal into 11-cis-retinal, which is crucial for the visual cycle, (4) phagocytosis of shed photoreceptor membranes, and (5) secretion of essential factors for the structural integrity of the retina. An overview of these functions will be given. Most of the research on the physiopathology of diabetic retinopathy has been focused on the impairment of the neuroretina and the breakdown of the inner BRB. By contrast, the effects of diabetes on the RPE and in particular on its secretory activity have received less attention. In this regard, new therapeutic strategies addressed to modulating RPE impairment are warranted.

Topics: Animals; Antioxidants; Blood-Retinal Barrier; Diabetic Retinopathy; Humans; Ions; Light; Models, Biological; Oxidative Stress; Oxygen; Phagocytosis; Photochemistry; Retinal Pigment Epithelium; Retinaldehyde; Water

Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness among the working-age population. Diabetic patients often experience functional deficits in dark adaptation, contrast sensitivity, and color perception before any microvascular pathologies on the fundus become detectable. Previous studies showed that the regeneration of 11-cis-retinal and visual pigment is impaired in a type 1 diabetes animal model, which negatively affects visual function at the early stage of DR. Here, Akita mice, type 1 diabetic model, were treated with the visual pigment chromophore, 9-cis-retinal. This treatment rescued a- and b-wave amplitudes of scotopic electroretinography responses, compared with vehicle-treated Akita mice. In addition, the administration of 9-cis-retinal alleviated oxidative stress significantly as shown by reduced 3-nitrotyrosine levels in the retina of Akita mice. Furthermore, the 9-cis-retinal treatment decreased retinal apoptosis as shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and DNA fragment enzyme-linked immunosorbent assay. Overall, these findings showed that 9-cis-retinal administration restored visual pigment formation and decreased oxidative stress and retinal degeneration, which resulted in improved visual function in diabetic mice, suggesting that chromophore deficiency plays a causative role in visual defects in early DR.

Topics: Animals; Apoptosis; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Diterpenes; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Oxidative Stress; Retina; Retinaldehyde

Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Herein, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a- and b-wave amplitudes of scotopic and photopic electroretinography responses 4 months after diabetes induction compared to nondiabetic controls. Although Western blot analysis revealed no difference in opsin expression, rhodopsin content was decreased in diabetic retinas, as shown by a difference in absorbance. Consistently, levels of 11-cis-retinal, the chromophore for visual pigments, were significantly lower in diabetic retinas compared to those in controls, suggesting a retinoid deficiency. Among visual cycle proteins, interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6 protein showed significantly lower levels in diabetic rats than those in nondiabetic controls. Similarly, serum levels of retinol-binding protein 4 and retinoids were significantly lower in diabetic rats. Overall, these results suggest that retinoid metabolism in the eye is impaired in type 1 diabetes, which leads to deficient generation of visual pigments and neural retinal dysfunction in early diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Disease Models, Animal; Male; Photoreceptor Cells, Vertebrate; Rats, Wistar; Retina; Retinaldehyde; Retinol-Binding Proteins, Plasma; Rhodopsin; Visual Pathways

To test the hypothesis that in dark-adapted diabetic mice subnormal manganese uptake in the outer retina can be ameliorated with exogenous 11-cis-retinal intervention.. Three groups were studied: age-matched controls and mice that had been diabetic for 3 months with and without acute, systemic 11-cis-retinal treatment administered 30 min before the manganese injection. Mice in each group were examined with manganese-enhanced magnetic resonance imaging (MEMRI) to assess central intraretinal manganese uptake and extraocular muscle manganese uptake. Bodyweights and glycated hemoglobin were determined.. Both diabetic groups had lower bodyweights and higher glycated hemoglobin levels relative to controls; no differences in these parameters between diabetic groups were noted. No substantial differences in muscle uptake were noted between any of the groups. Diabetes produced a subnormal intraretinal uptake of manganese; acute exogenous 11-cis-retinal significantly corrected only outer retinal uptake, although not to control levels.. The present results provide for the first time evidence that raises the possibility of a critical role of 11-cis-retinal, a key participant of the visual cycle, in diabetes-evoked outer retinal dysfunction.

Topics: Animals; Body Weight; Dark Adaptation; Diabetic Retinopathy; Glycated Hemoglobin; Ion Channels; Ion Transport; Magnetic Resonance Imaging; Male; Manganese; Mice; Mice, Inbred C57BL; Retina; Retinaldehyde

In diabetes, retinal vascular basement membrane (BM) undergoes significant thickening and compromises vessel function including increased vascular permeability, a prominent lesion of early diabetic retinopathy. In this study we determined whether altered expression and activity of lysyl oxidase (LOX), a cross-linking enzyme, may compromise vascular basement membrane functional integrity under high-glucose (HG) conditions.. Rat retinal endothelial cells (RRECs) grown in normal (5 mmol/l) or HG (30 mmol/l glucose) medium for 7 days were assessed for expression of LOX and proLOX by Western blot analysis and LOX enzyme activity. To determine whether HG alters cellular distribution patterns of LOX and proLOX, immunostaining with respective antibodies was performed. Similarly, cells grown in normal or HG medium were subjected to both LOX inhibition with β-aminopropionitrile (BAPN) and by small interfering RNA knockdown, and respectively examined for cell monolayer permeability. Additionally, retinas of streptozotocin (STZ)-induced diabetic rats were analyzed to determine if diabetes altered LOX expression.. Western blot analysis revealed significantly increased LOX and proLOX expression in cells grown in HG medium compared with those grown in normal medium. The increased LOX level was strikingly similar to LOX upegulation in the diabetic retinas. In cells grown in HG medium, LOX activity and cell monolayer permeability was significantly increased, as were LOX and proLOX immunostaining. Small interfering RNA- or BAPN-induced-specific blockage of LOX expression or activity, respectively, reduced cell monolayer permeability.. HG-induced increased LOX expression and activity compromises barrier functional integrity, a prominent lesion of diabetic retinopathy.

Topics: Aminopropionitrile; Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelial Cells; Endothelium, Vascular; Extracellular Matrix; Glucose; Male; Protein-Lysine 6-Oxidase; Rats; Rats, Sprague-Dawley; Retina; Retinaldehyde