New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

Park, Young Gun; Roh, Yong Kyun

doi:10.1155/2016/1753584

Cited by 37 publications

(31 citation statements)

References 67 publications

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“…Moreover, the current standard of care (e.g., anti-VEGF therapy and panretinal photocoagulation) is focused on halting late stage disease progression. 5,54,55 However, more recent studies include research on earlier and preclinical hallmarks of DR, such as inflammation and neurodegeneration. These pathologic processes possibly even precede the vascular phase and might be crucial factors that lie at the onset of the development of sight-threatening PDR and macular edema.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Sergeys

Étienne

Hove

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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The goal of this study was to perform an extensive temporal characterization of the early pathologic processes in the streptozotocin (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the vascular phenotype, and to investigate the potential of clinically relevant compounds in attenuating these processes. METHODS. Visual acuity and contrast sensitivity (CS) were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, spectral domain optical coherence tomography (SD-OCT), leukostasis, and immunohistochemistry were applied to investigate neurodegeneration, inflammation, and gliosis during early-, mid-and late-phase diabetes. Aflibercept or triamcinolone acetonide (TAAC) was administered to investigate their efficacy on the aforementioned processes. RESULTS. Visual acuity and CS loss started at 4 and 18 weeks postdiabetes onset, respectively, and progressively declined over time. ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical analyses linked these findings to retinal ganglion and cholinergic amacrine cell loss at 4 and 8 weeks postdiabetes onset, respectively, which was further decreased after aflibercept administration. The number of adherent leukocytes was augmented after 2 weeks, whereas increased micro-and macroglia reactivity was present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy on inflammation and gliosis. CONCLUSIONS. STZ-induced diabetic mice developed early pathologic DR hallmarks, from which inflammation seemed the initial trigger, leading to further development of functional and morphologic retinal changes. These findings indicate that the mouse STZ model is suitable to study novel integrative non-vascular therapies to treat early DR.

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Section: Discussionmentioning

confidence: 99%

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Sergeys

Étienne

Hove

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…Thus, if instituted early, given modeling induction of retinal environment either by production of mediators such as PEDF, or by activation of microglia and medullary cells with reparative functions recruitment, it can prevent disease progression, even though it does not restore visual acuity [Park and Roh, ]. Nowadays, it is the major therapeutic methodology used for patients exhibiting a high risk of blindness—PDR or clinically significant diabetic macular edema (CSME) [Park and Roh, ]. There are studies that refer to its impact in reduction severe vision impairment in eyes at high risk [Ben‐Av et al, ].…”

Section: Current Therapeutic Of Drmentioning

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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“…Potentially deleterious consequences of administering Ang-1 for prolonged periods include unwanted angiogenesis and potential promotion of tumors [21]. Several novel intravitreal medications and dexamethasone implants have provided promising therapeutic options [23,24]. …”

Section: Introductionmentioning

confidence: 99%

Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

et al. 2016

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Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown.

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New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

Cited by 37 publications

References 67 publications

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

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