Microvascular Complications and Diabetic Retinopathy: Recent Advances and Future Implications

Barot, Megha; Gokulgandhi, Mitan; Patel, Sulabh; Mitra, Ashim K.

doi:10.4155/fmc.12.206

Cited by 75 publications

(55 citation statements)

References 126 publications

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“…In earlier DR, there is decrease of retinal perfusion caused by the constriction of arterial vasculature retinal and consequent induction of a series of alterations [Barot et al, ]. Thickening of the vascular basal membrane is present due to the alteration of tight junctions, apoptosis of pericytes and endothelial cells, which become the earliest development of histological changes in DR [Alder et al, ].…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Capitão

Soares

2016

J of Cellular Biochemistry

267

190

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Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes and one of the most frequent causes of blindness in active age. Etiopathogenesis behind this important complication is related to several biochemical, hemodynamic and endocrine mechanisms with a preponderant initial role assumed by polyol pathways, increment of growth factors, accumulation of advanced glycation end products (AGE), activation of protein kinase C (PKC), activation of the renin-angiotensin-aldosterone system (RAAS), and leukostasis. Chronic and sustained hyperglycemia works as a trigger to the early alterations that culminate in vascular dysfunction. Hypoxia also plays an essential role in disease progression with promotion of neovascularization and vascular dystrophies with vitreous hemorrhages induction. Thus, the accumulation of fluids and protein exudates in ocular cavities leads to an opacity augmentation of the cornea that associated to neurodegeneration results in vision loss, being this a devastating characteristic of the disease final stage. During disease progression, inflammatory molecules are produced and angiogenesis occur. Furthermore, VEGF is overexpressed by the maintained hyperglycemic environment and up-regulated by tissue hypoxia. Also pro-inflammatory mediators regulated by cytokines, such as tumor necrosis factor (TNF-α) and interleukin-1 beta (IL-1β), and growth factors leads to the progression of these processes, culminating in vasopermeability (diabetes macular edema) and/or pathological angiogenesis (proliferative diabetic retinopathy). It was found a mutual contribution between inflammation and angiogenesis along the process. J. Cell. Biochem. 117: 2443-2453, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Diabetic Retinopathymentioning

confidence: 99%

Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Capitão

Soares

2016

J of Cellular Biochemistry

267

190

View full text Add to dashboard Cite

show abstract

“…With the improvement of people's living standards, the incidence of diabetes has increased in developed and developing countries, including China [ 1 ]. Patients who suffer from diabetes for a long time likely experience chronic vascular injury caused by high blood sugar levels; these patients are also at risk of DR when chronic vascular injury occurs in the retina [ 2 , 3 ]. The pathogenesis of DR is generally divided into two stages, namely, nonproliferative DR (NPDR) and proliferative DR (PDR).…”

Section: Introductionmentioning

confidence: 99%

“…The pathogenesis of DR is generally divided into two stages, namely, nonproliferative DR (NPDR) and proliferative DR (PDR). In early NPDR stage, DR is characterized by retinal blood vessel permeability as a result of damaged blood retinal barrier (BRB); in PDR stage, retinal neoangiogenesis occurs [ 2 , 3 ]. Previous studies have demonstrated that both inflammation and angiogenesis play important roles in regulating the development of DR, and thus anti-inflammation and antiangiogenesis are potential therapeutic strategies for the treatment of DR [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Dendrobium chrysotoxumLindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

Gong

Lü

et al. 2015

Journal of Diabetes Research

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Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1.

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“…Neovascularization is the most common pathology in many blinding disorders including wet age-related macular degeneration (AMD) [1], macular edema (ME) and proliferative diabetic retinopathy (DR) [2]. Retinal microvascular changes have been observed during these complications, which are attributed to retinal vulnerability towards subtle pathological alterations.…”

Section: Introductionmentioning

confidence: 99%

Novel Thermosensitive Pentablock Copolymers for Sustained Delivery of Proteins in the Treatment of Posterior Segment Diseases

Patel¹,

Vaishya²,

Yang³

et al. 2014

PPL

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Biodegradable and injectable in situ thermosensitive hydrogels were investigated for sustained delivery of protein therapeutics in the treatment of ocular posterior segment neovascular diseases. A series of triblock (TB, polycaprolac-tone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL), B-A-B) and pentablock copolymers (PBCs) (polylactic acid (PLA)-PCL-PEG-PCL-PLA (C-B-A-B-C) and PEG-PCL-PLA-PCL-PEG (A-B-C-B-A)) were synthesized and evaluated for their thermosensitive behavior. Effects of molecular weight, hydrophobicity and block arrangement on polymer crystallinity, sol-gel transition, micelle size, viscosity and in vitro drug release were examined. Results from sol-gel transition studies demonstrated that aqueous solutions of block copolymers can immediately transform to hydrogel upon exposure to physiological temperature. PBC provide significantly longer sustained release (more than 20 days) of IgG relative to TB copolymers. Moreover, kinematic viscosity of aqueous solution at 25°C for A-B-C-B-A type of PBCs was noticeably lower than the TB (B-A-B) copolymers and other PBCs with C-B-A-B-C block arrangements suggesting desired syringeability. The presence of PLA blocks in PBCs (C-B-A-B-C and A-B-C-B-A) significantly reduces crystallinity. Hence, it is anticipated that PBCs will have a faster rate of degradation relative to PCL-PEG-PCL based TB copolymers. PBCs also exhibited excellent cell viability and biocompatibility on ARPE-19 (human retinal pigment epithelial cell line) and RAW-264.7 (mouse macrophage cells), likely rendering it safe for ocular applications. Owing to biodegradability, thermosensitivity, ease of handling and biocompatibility PBC hydrogels can be considered as promising biomaterial for sustained delivery of protein therapeutics to the back of the eye.

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Microvascular Complications and Diabetic Retinopathy: Recent Advances and Future Implications

Cited by 75 publications

References 126 publications

Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Dendrobium chrysotoxumLindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

Novel Thermosensitive Pentablock Copolymers for Sustained Delivery of Proteins in the Treatment of Posterior Segment Diseases

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