scholarly journals Early Microglial Changes Associated with Diabetic Retinopathy in Rats with Streptozotocin-Induced Diabetes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Young Gun Park ◽  
Ji-Yeon Lee ◽  
Chongtae Kim ◽  
Young-Hoon Park
Keyword(s):  
Diabetic Retinopathy ◽  
Microglial Activation ◽  
Early Stage ◽  
Morphological Changes ◽  
Disease Onset ◽  
Plexiform Layer ◽  
Diabetic Rats ◽  
Inner Plexiform Layer ◽  
Sprague Dawley ◽  
Early Stages

Although morphological changes in microglia have been reported to be associated with diabetic retinopathy, little is known about the early changes in the microglia and macrophages during the progression of this condition. The present study was aimed at characterizing retinal microglial activation in the early stages of experimental diabetic retinopathy. Toward this end, a model of diabetic retinopathy was generated by intraperitoneally injecting male Sprague-Dawley rats with streptozotocin. No apparent histological changes were observed during the early stages of experimental diabetic retinopathy. However, at 4 to 16 weeks after the onset of diabetes, the retinas from diabetic rats exhibited higher density of microglia than those from age-matched normal controls, with microglial density peaking at 12 weeks. In particular, the proportion of the activated microglia increased significantly in the diabetic rats, specifically in the nerve fiber and ganglion cell layers, whereas it decreased in the inner plexiform layer within 12 weeks. Furthermore, the resident retinal microglial cells were activated immediately after diabetes induction, peaked at 12 weeks, and remained for up to 16 weeks after disease onset. Thus, experimental diabetic retinopathy causes gradual hypoxia and neuroinflammation, followed by the activation of microglia and the migration of macrophages. The distribution and density of retinal microglial activation changed typically with the progression of the disease in early-stage diabetic rats.

scholarly journals Visual acuity is correlated with ischemia and neurodegeneration in patients with early stages of diabetic retinopathy

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jin Li ◽  
Yue Zhou ◽  
Feng Chen ◽  
Yingzi Li ◽  
Rong Zhou ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Interactive Effect ◽  
Plexiform Layer ◽  
Vessel Density ◽  
Inner Plexiform Layer ◽  
Optical Coherence ◽  
Early Stages ◽  
Capillary Plexus

Abstract Purpose We investigated the effects of retinal ischemia, neurodegeneration, and subclinical edema on best-corrected visual acuity (BCVA) in the early stages of diabetic retinopathy (DR). Methods Ischemia was evaluated by the microvascular parameters measured by optical coherence tomography angiography. Neurodegeneration and subclinical edema were identified by the intraretinal layer thickness obtained by optical coherence tomography. Eyes with nonproliferative diabetic retinopathy (n = 132) from 89 patients were analyzed. Eyes were classified as having normal BCVA (n = 88 [66.7%], Snellen equivalent ≥ 20/20) or decreased BCVA (n = 44 [33.3%], Snellen equivalent < 20/20). The prevalence of ischemia, neurodegeneration, and subclinical edema was explored in patients with and without decreased BCVA, and correlations between BCVA and these pathological pathways were determined. Results Vessel density in the deep retinal capillary plexus (DRCP) and thickness of ganglion cell layer plus inner plexiform layer (GCL-IPL) were significantly lower in eyes with decreased BCVA compared with eyes with normal BCVA (both P < 0.05). In the final multiple regression predictive model, age, DRCP vessel density, and GCL-IPL thickness (all P ≤ 0.044) were predictors of BCVA. DRCP vessel density and GCL-IPL thickness have an interactive effect on visual acuity. The proportions of ischemia and neurodegeneration were significantly higher in eyes with decreased BCVA than in eyes with normal BCVA (P = 0.001 and P = 0.004, respectively). Conclusion During the natural course of the early stages of DR, ischemia and neurodegeneration were the main disease pathways associated with visual acuity, and the mechanisms varied among patients.

scholarly journals Fortified Extract of Red Berry,Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Claudio Bucolo ◽  
Giuseppina Marrazzo ◽  
Chiara Bianca Maria Platania ◽  
Filippo Drago ◽  
Gian Marco Leggio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Diabetic Retinopathy ◽  
Ginkgo Biloba ◽  
Plasma Lipid ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
White Willow ◽  
Willow Bark

Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries,Ginkgo bilobaand white willow bark containing carnosine andα-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-αand VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-αand VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

scholarly journals Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Chunyang Zhang ◽  
Yao Meng ◽  
Qi Liu ◽  
Miao Xuan ◽  
Lanyu Zhang ◽  
...  
Keyword(s):  
Surface Layer ◽  
Particle Density ◽  
Early Stage ◽  
Diabetic Rats ◽  
Mesangial Matrix ◽  
Sprague Dawley ◽  
Endothelial Surface Layer ◽  
Sprague Dawley Rats ◽  
Endothelial Surface

Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidencein vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

Macular thickness profile and diabetic retinopathy: the Singapore Epidemiology of Eye Diseases Study

2017 ◽  
Vol 102 (8) ◽  
pp. 1072-1076 ◽  
Author(s):  
Wei Dai ◽  
Yih Chung Tham ◽  
Ning Cheung ◽  
Masayuki Yasuda ◽  
Nicholas Y Q Tan ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Plexiform Layer ◽  
Glycated Haemoglobin ◽  
Eye Diseases ◽  
Inner Plexiform Layer ◽  
Outer Retina ◽  
Sd Oct

BackgroundTo evaluate retinal thickness profiles in eyes with and without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT) among individuals with diabetes.MethodsParticipants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians aged 40 years or older residing in Singapore. All participants underwent standardised systemic and ophthalmic examinations. Average thickness of the macula, ganglion cell-inner plexiform layer and outer retina layer (from the outer plexiform layer to the retinal pigment epithelium layer) were measured using SD-OCT. DR status and severity were graded based on fundus photographs using the modified Airlie House classification system. Participants with macular oedema were excluded.Results2240 eyes from 1280 participants were included. Of these, 1764 (78.7%) eyes had no DR, 351 (15.7%) eyes had minimal or mild DR and 125 (5.6%) eyes had moderate or worse DR. After adjusting for age, gender, ethnicity, axial length, hypertension, glycated haemoglobin, body mass index, total cholesterol and diabetes duration, eyes with DR had thicker macula (245.44 µm vs 243.04 µm, P=0.03) and outer retina (124.26 µm vs 123.08 µm, P=0.01) than eyes without DR. When stratified by DR severity, thicker macula (250.24 µm vs 242.88 µm, P=0.011) and outer retina (126.4 µm vs 123.0 μm, P=0.006) were observed in eyes with moderate or worse, but not minimal or mild DR, compared with eyes without DR.ConclusionsEven in the absence of macular oedema, eyes with DR, particularly those with more severe DR, had thicker macular and outer retinal layers than eyes without DR.

scholarly journals Nuclear PKR in retinal neurons in the early stage of diabetic retinopathy in streptozotocin‑induced diabetic rats

2021 ◽  
Vol 24 (2) ◽  
Author(s):  
Viviane Silva ◽  
Nayara André ◽  
Thaís Sousa ◽  
Vâni Alves ◽  
Isis Kettelhut ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Early Stage ◽  
Diabetic Rats ◽  
Retinal Neurons

scholarly journals Superoxide dismutase 3 prevents early stage diabetic retinopathy in streptozotocin-induced diabetic rat model

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262396
Author(s):  
Ji-Yeon Lee ◽  
Mirinae Kim ◽  
Su Bin Oh ◽  
Hae-Young Kim ◽  
Chongtae Kim ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Diabetic Retinopathy ◽  
Rat Model ◽  
Treated Group ◽  
Diabetic Rats ◽  
Photopic Negative Response ◽  
Diabetic Rat ◽  
Control Group ◽  
Inner Plexiform Layer ◽  
Diabetic Rat Model

Purpose To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model. Methods Diabetic models were established by a single intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. After purification of the recombinant SOD3, intravitreal injection of SOD3 was performed at the time of STZ injection, and 1 and 2 weeks following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with ɑ-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), pigment epithelium-derived factor (PEDF), Flt1, recoverin, parvalbumin, extracellular superoxide dismutase (SOD3), 8-Hydroxy-2’deoxyguanosine (8-OHdG) and tumor necrosis factor-ɑ (TNF-ɑ) were evaluated. Results In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 8 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the SOD3 treated group. GFAP, Flt1, 8-OHdG and TNF-ɑ immunoreactivity were increased, and ɑ-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the SOD3 treated group. Parvalbumin expression was not decreased in the SOD3 treated group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the SOD3 treated group. Conclusions SOD3 treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. We also suggest that in rod-dominant rodents, the use of blue on green photopic negative response (PhNR) is effective in measuring the inner retinal function in animal models of diabetic retinopathy. SOD3 treatment ameliorated the retinal Müller cell activation in diabetic rats and pericyte dysfunction. These results suggested that SOD3 exerted protective effects on the development of diabetic retinopathy.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 556 ◽  
Author(s):  
Muhammad Zulfiqah Sadikan ◽  
Nurul Alimah Abdul Nasir ◽  
Renu Agarwal ◽  
Nafeeza Mohd Ismail
Keyword(s):  
Diabetic Retinopathy ◽  
Topical Treatment ◽  
Cell Apoptosis ◽  
Experimental Period ◽  
Diabetic Rats ◽  
Retinal Cell ◽  
Retinal Layer ◽  
Sprague Dawley ◽  
Vegf Expression ◽  
Tocotrienol Rich Fraction

Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.

scholarly journals Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats

2001 ◽  
Vol 281 (1) ◽  
pp. R239-R245 ◽  
Author(s):  
Kaushik P. Patel ◽  
Pamela K. Carmines
Keyword(s):  
Hydrostatic Pressure ◽  
Volume Expansion ◽  
Renal Denervation ◽  
Early Stage ◽  
Isotonic Saline ◽  
Diabetic Rats ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Interstitial Volume ◽  
Sprague Dawley Rats

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na+ excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Δ = 12.2 ± 2.4 mmHg), urine flow (Δ = 54 ± 8 μl · min−1 · g−1), and Na+ excretion (Δ = 11.5 ± 1.9 μeq · min−1 · g−1). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na+excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na+ excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na+ excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.

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