scholarly journals Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3265
Author(s):  
Nicole Schmitner ◽  
Christina Recheis ◽  
Jakob Thönig ◽  
Robin A. Kimmel

Diabetic retinopathy is a frequent complication of longstanding diabetes, which comprises a complex interplay of microvascular abnormalities and neurodegeneration. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 display a diabetic phenotype with survival into adulthood, and are therefore uniquely suitable among zebrafish models for studying pathologies associated with persistent diabetic conditions. We have previously shown that, starting at three months of age, pdx1 mutants exhibit not only vascular but also neuro-retinal pathologies manifesting as photoreceptor dysfunction and loss, similar to human diabetic retinopathy. Here, we further characterize injury and regenerative responses and examine the effects on progenitor cell populations. Consistent with a negative impact of hyperglycemia on neurogenesis, stem cells of the ciliary marginal zone show an exacerbation of aging-related proliferative decline. In contrast to the robust Müller glial cell proliferation seen following acute retinal injury, the pdx1 mutant shows replenishment of both rod and cone photoreceptors from slow-cycling, neurod-expressing progenitors which first accumulate in the inner nuclear layer. Overall, we demonstrate a diabetic retinopathy model which shows pathological features of the human disease evolving alongside an ongoing restorative process that replaces lost photoreceptors, at the same time suggesting an unappreciated phenotypic continuum between multipotent and photoreceptor-committed progenitors.

2019 ◽  
Vol 8 (2S11) ◽  
pp. 3637-3640

Retinal vessels ID means to isolate the distinctive retinal configuration issues, either wide or restricted from fundus picture foundation, for example, optic circle, macula, and unusual sores. Retinal vessels recognizable proof investigations are drawing in increasingly more consideration today because of pivotal data contained in structure which is helpful for the identification and analysis of an assortment of retinal pathologies included yet not restricted to: Diabetic Retinopathy (DR), glaucoma, hypertension, and Age-related Macular Degeneration (AMD). With the advancement of right around two decades, the inventive methodologies applying PC supported systems for portioning retinal vessels winding up increasingly significant and coming nearer. Various kinds of retinal vessels segmentation strategies discussed by using Deep Learning methods. At that point, the pre-processing activities and the best in class strategies for retinal vessels distinguishing proof are presented.


2008 ◽  
Vol 33 (4) ◽  
pp. 385-393 ◽  
Author(s):  
Kirsten H. Eibl ◽  
Kerstin Schwabe ◽  
Ulrich Welge-Luessen ◽  
Anselm Kampik ◽  
Wolfram Eichler

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Maurizio Cammalleri ◽  
Massimo Dal Monte ◽  
Filippo Locri ◽  
Stefania Marsili ◽  
Liliana Lista ◽  
...  

The spontaneously diabetic Torii (SDT) rat is of increasing preclinical interest because of its similarities to human type 2 diabetic retinopathy (DR). The system formed by urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is a player in blood-retinal barrier (BRB) breakdown in DR. Here, we investigated whether in SDT rats, preventive administration of UPARANT, an inhibitor of the uPAR pathway, counteracts the retinal impairment in response to chronic hyperglycemia. Electroretinogram (ERG) monitoring was followed over time. Fluorescein-dextran microscopy, CD31 immunohistochemistry, quantitative PCR, ELISA, Evans blue perfusion, and Western blot were also used. UPARANT prevented ERG dysfunction, upregulation of vascular endothelial growth factor and fibroblast growth factor-2, BRB leakage, gliosis, and retinal cell death. The mechanisms underlying UPARANT benefits were studied comparing them with the acute streptozotocin (STZ) model in which UPARANT is known to inhibit DR signs. In SDT rats, but not in the STZ model, UPARANT downregulated the expression of uPAR and its membrane partners. In both models, UPARANT reduced the levels of transcription factors coupled to inflammation or inflammatory factors themselves. These findings may help to establish the uPAR system as putative target for the development of novel drugs that may prevent type 2 DR.


2022 ◽  
Vol 12 ◽  
Author(s):  
Etelka Pöstyéni ◽  
Alma Ganczer ◽  
Andrea Kovács-Valasek ◽  
Robert Gabriel

The mammalian retina contains approximately 30 neuropeptides that are synthetized by different neuronal cell populations, glia, and the pigmented epithelium. The presence of these neuropeptides leaves a mark on normal retinal molecular processes and physiology, and they are also crucial in fighting various pathologies (e.g., diabetic retinopathy, ischemia, age-related pathologies, glaucoma) because of their protective abilities. Retinal pathologies of different origin (metabolic, genetic) are extensively investigated by genetically manipulated in vivo mouse models that help us gain a better understanding of the molecular background of these pathomechanisms. These models offer opportunities to manipulate gene expression in different cell types to help reveal their roles in the preservation of retinal health or identify malfunction during diseases. In order to assess the current status of transgenic technologies available, we have conducted a literature survey focused on retinal disorders of metabolic origin, zooming in on the role of retinal neuropeptides in diabetic retinopathy and ischemia. First, we identified those neuropeptides that are most relevant to retinal pathologies in humans and the two clinically most relevant models, mice and rats. Then we continued our analysis with metabolic disorders, examining neuropeptide-related pathways leading to systemic or cellular damage and rescue. Last but not least, we reviewed the available literature on genetically modified mouse strains to understand how the manipulation of a single element of any given pathway (e.g., signal molecules, receptors, intracellular signaling pathways) could lead either to the worsening of disease conditions or, more frequently, to substantial improvements in retinal health. Most attention was given to studies which reported successful intervention against specific disorders. For these experiments, a detailed evaluation will be given and the possible role of converging intracellular pathways will be discussed. Using these converging intracellular pathways, curative effects of peptides could potentially be utilized in fighting metabolic retinal disorders.


2021 ◽  
Vol 3 (2) ◽  
pp. 66-74
Author(s):  
Naufallah Dinda Harumi ◽  
Ramzi Amin

Abstract Introduction.Diabetic retinopathy is a progressive microangiopathy characterized by damage and occlusion of small blood vessels. The earliest pathologic changes are thickening of the capillary endothelial basement membrane and a reduction in the number of pericits. Diabetic retinopathy is the main cause of vision loss in type 1 of DM patients and has various risk factors such as chronic hyperglycemia, hypertension, hypercholesterolemia, and elevated HbA1C levels. Methods.This research was conducted using a descriptive observational analytic method with a cross sectional approach at The Eye Polyclinic (RSUP) Dr. Mohammad Hoesin Palembang used secondary data on diabetic retinopathy patients. The sample consisted of 64 patients with a total sampling technique, there were 50 patients who met the inclusion criteria. Results.There was a significant relationship between HbA1C levels (p value = 0.050) with a PR value = 1.463 and total cholesterol (p value = 0.038) with a PR value = 1.667 for diabetic retinopathy. Conclusion.HbA1C levels and total cholesterol are significant risk factors for diabetic retinopathy.


Author(s):  
Roshana Devi Vellai ◽  
Subramanian Sorimuthu Pillai

Diabetic retinopathy (DR) is one of the earliest complications of chronic hyperglycemia and is a major cause of vision loss. Nearly all patients with type 1 diabetes mellitus and more than 60 % with chronic type 2 diabetes develop some degree of retinopathy after 10 years. Aldose reductase, the first enzyme in polyol pathway chiefly contributes to the development of diabetic retinopathy and other secondary complications. None of the currently available drugs used to inhibit the activity of aldose reductase is found to be ideal due to their adverse effects. Hence, the screening and identification of more effective and safer aldose reductase inhibitors from natural products have been critical requirement in the management and treatment of T2DM. Recently, we have reported the antidiabetic properties of phytochemicals such as Gymnemic acid, Trigonelline and Ferulic acid in high fat diet fed- low dose STZ induced experimental type 2 diabetes in rats. In the present study, the structure based computational method was employed to identify the in silico inhibitory effect of the above phytoingredients on aldose reductase activity. Auto Dock 4.2 is used to study the molecular interactions between the ligands and the receptor. The data obtained evidenced that the docking efficacy of the antidiabetic ligands which are comparable with fidarestat, the standard used in the present study. Thus, the antidiabetic properties of the above lead molecules may attribute to its aldose reductase inhibitory effect.


2020 ◽  
Author(s):  
Rehana Khan ◽  
Mahesh Shanmugam ◽  
Rajesh Ramanjulu ◽  
Jay Chablani ◽  
Niharika Singh ◽  
...  

Abstract Background: The supply of Cilioretinal artery (CRA) to different layers of retina influences retinal pathologies like diabetic retinopathy. Since the supply of CRA is segmental, Our aim is to analyze the location of CRA) with non center-involving and center-involving diabetic macular edema (DME) and to evaluate the supply of CRA with segments of macular edema based on Early Treatment of Diabetic Retinopathy Study (ETDRS) scale using optical coherence tomography (OCT).Design: Retrospective studyMethods: A retrospective study in which forty-three patients at various stages of diabetic retinopathy with the presence of CRA were identified. Presence and location of CRA was recognized using fundus fluorescein angiography. Classification of DME was based on ETDRS subfields on OCT.Results: Evaluation of 26 men and 17 women of various groups of diabetic retinopathy revealed unilateral CRA in 40 subjects and bilateral CRA in 3 subjects. When CRA supplied the central area, maximum retinal thickness was noted at the temporal quadrant (271.67±164.02 mm) and had non center-involving DME (194.87±121.06 mm), when CRA supplied the lower area, maximum retinal thickness was noted at the superior quadrant (293.64±159.36 mm) and had center-involving DME (395±285.75 mm), and when it supplied the upper area, maximum retinal thickness was noted at the nasal quadrant (293.49±176.18mm) with center-involving DME (292±192.79 mm).Conclusion: The presence of CRA seems to alter the morphology and influences the segment involved in DME. However, further studies with larger sample size are warranted to prove this association.


2020 ◽  
Author(s):  
Rajiv Raman ◽  
Rehana Khan ◽  
Mahesh Shanmugam ◽  
Rajesh Ramanjulu ◽  
Jay Chablani ◽  
...  

Abstract Background The supply of Cilioretinal artery (CRA) to different layers of retina influences retinal pathologies like diabetic retinopathy. Since the supply of CRA is segmental, Our aim is to analyze the location of CRA) with non center-involving and center-involving diabetic macular edema (DME) and to evaluate the supply of CRA with segments of macular edema based on Early Treatment of Diabetic Retinopathy Study (ETDRS) scale using optical coherence tomography (OCT). Design Retrospective study Methods and Materials A retrospective study in which forty-three patients at various stages of diabetic retinopathy with the presence of CRA were identified. Presence and location of CRA was recognized using fundus fluorescein angiography. Diabetic retinopathy was graded based on ETDRS classification using OCT. Results Evaluation of 26 men and 17 women of various groups of diabetic retinopathy revealed unilateral CRA in 40 subjects and bilateral CRA in 3 subjects. When CRA supplied the central area, maximum retinal thickness was noted at the temporal quadrant (271.67±164.02 μm) and had noncenter-involving DME (194.87±121.06 μm), when CRA supplied the lower area, maximum retinal thickness was noted at the superior quadrant (293.64±159.36 μm) and had center-involving DME (395±285.75 μm), and when it supplied the upper area, maximum retinal thickness was noted at the nasal quadrant (293.49±176.18μm) with center-involving DME (292±192.79 μm). Conclusion The presence of CRA seems to alter the morphology and influences the segment involved in DME. However, further studies with larger sample size are warranted to prove this association.


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