Diabetic Retinopathy: Important Biochemical Alterations and the Main Treatment Strategies

ValdezGuerrero, Amaranta Sarai; Quintana-Pérez, Julio César; Arellano-Mendoza, Mónica Griselda; Castañeda-Ibarra, Francisco Javier; Tamay‐Cach, Feliciano; Alemán-González-Duhart, Diana

doi:10.1016/j.jcjd.2020.10.009

Cited by 31 publications

(13 citation statements)

References 59 publications

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“…Current therapeutic strategies target the advanced stages of the disease and aim to slow its progression without really reversing its outcome [104]. Among the current treatments for proliferative DR and macular edema are laser photocoagulation, vitrectomy, and intravitreal injections of corticosteroids or anti-VEGF that could prevent further vision loss [105]. However, the curative activity of these treatments is limited by side effects.…”

Section: Kallikrein-kinin System In Diabetic Retinopathymentioning

confidence: 99%

Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Othman

Cagnone

Joyal

et al. 2021

Cells

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The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors are G-protein-coupled receptors that sense and mediate the effects of kinins. While B2R is constitutively expressed and regulates a plethora of physiological processes, B1R is almost undetectable under physiological conditions and contributes to pathological inflammation. Several KKS components (kininogens, tissue and plasma kallikreins, and kinin receptors) are overexpressed in human and animal models of retinal diseases, and their inhibition, particularly B1R, reduces inflammation and pathological neovascularization. In this review, we provide an overview of the KKS with emphasis on kinin receptors in the healthy retina and their detrimental roles in DR and AMD. We highlight the crosstalk between the KKS and the renin–angiotensin system (RAS), which is known to be detrimental in ocular pathologies. Targeting the KKS, particularly the B1R, is a promising therapy in retinal diseases, and B1R may represent an effector of the detrimental effects of RAS (Ang II-AT1R).

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Section: Kallikrein-kinin System In Diabetic Retinopathymentioning

confidence: 99%

Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Othman

Cagnone

Joyal

et al. 2021

Cells

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“…Several studies have shown that there is an increase of proinflammatory molecules in the retina or vitreous humor of diabetic animals and patients. Those reported are VEGF, TNF-α, iNOS, COX-2, prostacyclin, insulin-like growth factor 1, NF-κB, placental growth factor, intercellular adhesion molecule-1, IL-1β, IL-2, IL-6 and IL-8[ 81 , 84 - 86 ]. The findings highlight the key role of inflammation in the development of DR.…”

Section: Retinocellular Alterations In Diabetic Retinopathy Developmentmentioning

confidence: 99%

Cellular targets in diabetic retinopathy therapy

Rodriguez¹,

Millán²,

Ortega³

2021

WJD

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Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.

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“…Diabetes mellitus is a common metabolic disease characterized by hyperglycemia, which is related to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels, and nerves [ 1 , 2 ]. Diabetes mellitus is a global public health challenge, with a prevalence of about 10% in adults worldwide, and the International Diabetes Federation has predicted that there will be 592 million cases by 2035 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis

Wang

2022

Endocrinol Metab

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Background: This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model.Methods: Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice.Results: Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs.Conclusion: SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.

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Diabetic Retinopathy: Important Biochemical Alterations and the Main Treatment Strategies

Cited by 31 publications

References 59 publications

Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Cellular targets in diabetic retinopathy therapy

Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis

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