Retinal dysfunction parallels morphologic alterations and precede clinically detectable vascular alterations in Meriones shawi, a model of type 2 diabetes.

Diabetic retinopathy is a major cause of reduced visual acuity and acquired blindness. The aim of this work was to analyze functional and vascular changes in diabetic Meriones shawi (M.sh) an animal model of metabolic syndrome and type 2 diabetes. The animals were divided into four groups. Two groups were fed a high fat diet (HFD) for 3 and 7 months, two other groups served as age-matched controls. Retinal function was assessed using full field electroretinogram (Ff-ERG). Retinal thickness and vasculature were examined by optical coherence tomography, eye fundus and fluorescein angiography. Immunohistochemistry was used to examine key proteins of glutamate metabolism and synaptic transmission. Diabetic animals exhibited significantly delayed scotopic and photopic ERG responses and decreases in scotopic and photopic a- and b-wave amplitudes at both time points. Furthermore, a decrease of the amplitude of the flicker response and variable changes in the scotopic and photopic oscillatory potentials was reported. A significant decrease in retinal thickness was observed. No evident change in the visual streak area and no sign of vascular abnormality was present; however, some exudates in the periphery were visible in 7 months diabetic animals. Imunohistochemistry detected a decrease in the expression of glutamate synthetase, vesicular glutamate transporter 1 and synaptophysin proteins. Results indicate that a significant retinal dysfunction was present in the HFD induced diabetes involving both rod and cone pathways and this dysfunction correlate well with the morphological abnormalities reported previously. Furthermore, neurodegeneration and abnormalities in retinal function occur before vascular alterations would be detectable in diabetic M.sh.

Behaviour of Tunisian Psammomys obesus fed high-calorie diets: biochemical disturbance and histopathological alterations.

This work investigated the biochemical disturbances and histological alteration in Psammomys obesus animal model fed different high calorie diets (HCDs) during three months. Four diets were used: a low-calorie natural diet, Chenopodiaceae halophyte plant used as control (LCD), a high standard carbohydrate diet rich in protein, HCD 0, a high carbohydrate diet rich in two concentrations of fat, HCD 1 and HCD 2. All animals having received HCDs developed dyslipidemia after one month of experiment with distinction of different sub-groups developing or not obesity and diabetes. HCDs induced a remarkable increasing in blood cholesterol, LDL-cholesterol and triglyceride levels indicating a fast induction of dyslipidemia and a significant increase of aminotransaminases activities revealing a pronounced hepatotoxicity. Animal developing diabetes showed a severe hepatic injury, a degeneration of the adipose tissue and a significant reduction of retinal thickness. P. obesus seems to be an excellent animal model to investigate nutritional metabolic diseases.

Anti-Obesity and Anti-Dyslipidemic Effects of Salicornia arabica Decocted Extract in Tunisian Psammomys obesus Fed a High-Calorie Diet.

Salicornia is a halophyte plant that has been used in traditional medicine for the treatment of scurvy, goiter, and hypertension. It is commercialized in Europe and Asia as fresh salads, pickled vegetables, green salt, or tea powder. This work is the first to assess the potential anti-obesity and anti-dyslipidemic effects of Salicornia arabica decocted extract (SADE). SADE was characterized by its significant in vitro radical scavenging activity (using DPPH and ABTS assays). The effect of SADE on food intake, weight loss, serum biochemical parameters, liver and kidney weights, adiposity index and on liver histology was investigated in the Tunisian gerbil Psammomys obesus (P. obesus), which is recognized as a relevant animal model of human obesity and diabetes. P. obesus animals were firstly randomly divided into two groups: the first received a natural low-calorie chow diet (LCD), and the second group received a high-calorie diet (HCD) over 12 weeks. On day 90, animals were divided into four groups receiving or not receiving SADE (LCD, LCD + SADE, HCD, and HCD + SADE). If compared to the HCD group, SADE oral administration (300 mg/kg per day during 4 weeks) in HCD + SADE group showed on day 120 a significant decrease in body weight (-34%), blood glucose (-47.85%), serum levels of total cholesterol (-54.92%), LDL cholesterol (-60%), triglycerides (-48.03%), and of the levels of hepatic enzymes: ASAT (-66.28%) and ALAT (-31.87%). Oral administration of SADE restored the relative liver weight and adiposity index and significantly limited HCD-induced hepatic injury in P. obesus. SADE seems to have promising in vivo anti-obesity and anti-dyslipidemic effects.

Effects of humic acid and organic acids supplements on performance, meat quality, leukocyte count, and histopathological changes in spleen and liver of broiler chickens.

The aim of the present study is to evaluate the effect of Humic Acid (HA), Organic Acids (OA), and their combination (HAOA) on the growth performance, meat quality, leukocyte count, and histopathological changes in the liver and spleen of broiler chickens. A total of 2100 one-day-old mix-sexed broiler chickens were randomly divided into 4 groups with 5 replicates per treatment using 105 birds per pen (pen is used as an experimental unit). Treatments were: 1) Control (basal diet without additives), 2) Basal diet +0.1% HA, 3) Basel diet +0.1% HA+ 0.02% OA, 4) Basel diet +0.02% OA. Growth performance was not significantly affected by all dietary treatments during the experiment period. Sensory evaluation of breast meat indicated a significant positive response for color and smell corresponding to treatment 2) Basal diet +0.1% HA and treatment 3) Basel diet +0.1% HA+ 0.02% OA (P < 0.05). Birds receiving HA and HAOA developed fewer hepatic lesions compared to the control group (P < 0.05) and showed normal spleen structure with the extension of the white pulp area. Supplementation of HAOA corresponds to a lower heterophil to lymphocyte (H/L) ratio. The combination of HA and OA improves sensory attributes of cooked breast meat, H/L ratio, and preserves the histological structure of the spleen and liver of broiler chickens. HAOA can be recommended as a combined feed additive to improve broiler chickens' health.

Neuroprotective effects of oleuropein on retina photoreceptors cells primary culture and olive leaf extract and oleuropein inhibitory effects on aldose reductase in a diabetic model: Meriones shawi.

Aldose reductase (AR) is an enzyme implicated in the development of diabetes complications among them diabetic retinopathy. Erythrocyte AR activity was measured in control and diabetic Meriones shawi, a type-2 diabetic model. We noticed an increase of AR activity in diabetic Meriones by comparison to controls. Olive leaf aqueous extract and oleuropein were tested for their inhibitory potential on AR activity. Both exerted a partial in-vitro inhibition effect which was higher with the olive leaf extract. The ex-vivo protective effect of oleuropein was tested in photoreceptors rod and Mcône retinal cells of Meriones shawi in hyperglycaemic conditions. Mixed retinal cells were cultured at 25 mM glucose for 5 days and treated with oleuropein. Cell viability was assessed using MTT test and trypan blue exclusion dye. Rod and Mcône Photoreceptors were characterised by immuno-cytochemistry. Oleuropein protected retinal cells against the toxic effect of glucose by improving the viability of photoreceptors.

Short-Term Administration of Astaxanthin Attenuates Retinal Changes in Diet-Induced Diabetic Psammomys obesus.

OBJECTIVES: Psammomys obesus is a high-fat diet (HFD)-fed animal model of obesity and type 2 diabetes recently explored as a model of non-proliferative diabetic retinopathy. This study tested the protective effect of the pigment astaxanthin (AST) in the P. obesus diabetic retina. METHODS: Young adult P. obesus were randomly assigned to two groups. The control group received a normal diet consisting of a plant-based regimen, and the HFD group received an enriched laboratory chow. After 3 months, control and diabetic rodents were administered vehicle or AST, daily for 7 days. Body weight, blood glucose, and plasma pentosidine were assessed. Frozen sections of retinas were immunolabeled for markers of oxidative stress, glial reactivity and retinal ganglion cell bodies, and imaged by confocal microscopy. RESULTS: Retinal tissue from AST-treated control and HFD-diabetic P. obesus showed a greater expression of the antioxidant enzyme heme oxygenase-1 (HO-1). In retinas of HFD-diabetic AST-treated P. obesus, cellular retinaldehyde binding protein and glutamine synthetase in Müller cells were more intense compared to the untreated HFD-diabetic group. HFD-induced diabetes downregulated the expression of glial fibrillary acidic protein in astrocytes, the POU domain protein 3A in retinal ganglion cells, and synaptophysin throughout the plexiform layers. DISCUSSION: Our results show that type 2-like diabetes induced by HFD affected glial and neuronal retinal cell homeostasis. AST treatment induced the antioxidant enzyme HO-1 and reduced glial reactivity. These findings suggest that diabetic P. obesus is a useful model of HFD-induced obesity and diabetes to evaluate early neuroglial retinal alterations and antioxidant neuroprotection mechanisms in DR.

Electroretinographic evidence suggesting that the type 2 diabetic retinopathy of the sand rat Psammomys obesus is comparable to that of humans.

PURPOSE: Type 2 diabetic retinopathy is the main cause of acquired blindness in adults. The aim of this work was to examine the retinal function of the sand rat Psammomys obesus as an animal model of diet-induced type 2 diabetes when subjected to a hypercaloric regimen. MATERIALS AND METHODS: Hyperglycemia was induced in Psammomys obesus by high caloric diet (4 kcal/g). The visual function of control (n = 7) and diabetic (n = 7) adult rodents were followed up during 28 consecutive weeks with full-field electroretinogram(ERG) recordings evoked to flashes of white light according to the standard protocol of the International Society for Clinical Electrophysiology of Vision protocol (ISCEV). RESULTS: Twenty-eight weeks following the induction of diabetes, results revealed significantly reduced and delayed photopic and scotopic ERG responses in diabetic rats compared to control rats. More specifically, we noted a significant decrease in the amplitude of the dark-adapted 0.01ERG (62%), a- and b-wave amplitudes of the dark-adapted 3.0 ERG (33.6%, 55.1%) and the four major oscillatory potentials components (OP1-OP4) (39.0%, 75.2%, 54.8% and 53.7% respectively). In photopic conditions, diabetic rats showed a significant decrease in a- and b-wave (30.4%, 43.4%), photopic negative response (55.3%), 30 Hz flicker (63.7%), OP1-OP4(51.6%, 61.8%, 68.3% and 47.5% respectively) and S-cone (34.7%). Significantly delayed implicit times were observed for all ERG components in the diabetic animals. Results obtained are comparable to those characterizing the retinal function of patients affected with advanced stage of diabetic retinopathy. CONCLUSION: Psammomys obesus is a useful translational model to study the pathophysiology of diabetic retinopathy in order to explore new therapeutic avenues in human patients.

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.