Cell Therapy for Diabetic Retinopathy—A Work in Progress

2012 ◽  
Vol 08 (01) ◽  
pp. 45
Author(s):  
David Kent ◽  

As the incidence of diabetes continues to rise worldwide, the challenge in preventing vision loss secondary to diabetic retinopathy (DR) remains a formidable one. Current treatments are only indicated in advanced disease when vision loss is imminent or has already occurred. In recent years, due to the discovery that post-natal vasculogenesis plays a role in vascular repair, there has been increasing optimism that cell therapy using endothelial progenitor cells (EPCs) can be harnessed therapeutically for conditions such as DR. Although autologous EPC therapy offers promise for DR, EPCs from patients with diabetes are themselves dysfunctional, while the diabetic milieu itself contributes further to this dysfunctionality. Additional research is required to unravel the complete science of vasculogenesis and the role of EPCs in repair, so that treatment can be optimized in terms of actual cell choice, pre-conditioning prior to transplantation, maximizing cell survival in the recipient, and preparation of the recipient tissue to ensure an adequate therapeutic response.

2012 ◽  
Vol 06 (02) ◽  
pp. 125
Author(s):  
David Kent ◽  

As the incidence of diabetes continues to rise worldwide, the challenge in preventing vision loss secondary to diabetic retinopathy (DR) remains a formidable one. Current treatments are only indicated in advanced disease when vision loss is imminent or has already occurred. In recent years, due to the discovery that postnatal vasculogenesis plays a role in vascular repair, there is increasing optimism that cell therapy using endothelial progenitor cells (EPCs) can be harnessed therapeutically for conditions such as DR. Although autologous EPC therapy offers promise for DR, EPCs from patients with diabetes are themselves dysfunctional while the diabetic milieu itself contributes further to this dysfunctionality. Additional research is also required to unravel the complete science of vasculogenesis and the role of EPCs in repair so that treatment can be optimised in terms of actual cell choice, pre-conditioning prior to transplantation, maximising cell survival in the recipient and preparation of the recipient tissue to ensure an adequate therapeutic response.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1683
Author(s):  
Milagros Mateos-Olivares ◽  
Luis García-Onrubia ◽  
Fco. Javier Valentín-Bravo ◽  
Rogelio González-Sarmiento ◽  
Maribel Lopez-Galvez ◽  
...  

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.


2020 ◽  
Vol 10 (8) ◽  
pp. 2777
Author(s):  
Eliana B. Souto ◽  
Joana R. Campos ◽  
Raquel Da Ana ◽  
Joana F. Fangueiro ◽  
Carlos Martins-Gomes ◽  
...  

Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.


2011 ◽  
Vol 36 (4) ◽  
pp. 247 ◽  
Author(s):  
Praveen Vashist ◽  
Noopur Gupta ◽  
Sameeksha Singh ◽  
Rohit Saxena

2014 ◽  
Vol 10 (01) ◽  
pp. 25
Author(s):  
Lauren M Marozas ◽  
Patrice E Fort ◽  
◽  

Diabetic retinopathy is the major ocular complication associated with diabetes, and represents the leading cause of legal blindness in the working-age population of developed countries. Although classically diagnosed based on abnormalities of the retinal microvasculature, diabetic retinopathy is now widely recognized as a neurovascular disease. While all patients with diabetes are at increased risk for eye disease including diabetic retinopathy, proactive measures, and timely intervention can prevent or delay subsequent vision loss. Systemic management of diabetes by combined control of glycemia, blood pressure, and serum lipid levels remains the most important method of preventing diabetic retinopathy onset and progression. Once detected, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection can help preserve vision. However, the need for improved detection methods and therapies that will allow earlier diagnosis and treatment remains apparent. This review summarizes current techniques for the prevention and intervention for diabetic retinopathy, and examines ongoing developments in the search for new endpoints and therapies as they apply to preventing vision loss associated with diabetes.


Author(s):  
Liang Zhu ◽  
Robert Flower

Diabetic retinopathy refers to diabetes-related complications in the retina, It is a progressive disease and its symptoms in the eyes can vary from non-vision threatening to vision loss, and it can lead to permanent damage to the neuronal retinal tissue. The irreversible nature of the damage suggests that prevention of diabetes by eliminating risk factors and early screening are the cornerstone of relevant treatment to stop or limit visual damage in those patients.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jorge S. Andrade Romo ◽  
Giselle Lynch ◽  
Kevin Liu ◽  
Daniel Kim ◽  
Michael Jansen ◽  
...  

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r=0.98 (p=0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r=0.688) was not found to be significant (p=0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.


2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S9-S11 ◽  
Author(s):  
Paul M Dodson

Diabetic eye disease is the major cause of blindness and vision loss among working-age people in developed countries. Microangiopathy and capillary occlusion underlie the pathogenesis of disease. While laser treatment is regarded as the standard therapy, intensive medical management of glycaemia and hypertension is also a priority in order to reduce the risk of diabetic retinopathy. Recent data have prompted a re-evaluation of the role of lipid-modifying therapy in reducing diabetic retinopathy. The Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study demonstrated a significant 30% relative reduction in the need for first retinal laser therapy in patients with (predominantly early-stage) type 2 diabetes treated with fenofibrate 200 mg daily, from 5.2% with placebo to 3.6% with fenofibrate, p=0.0003. The benefit of fenofibrate was evident within the first year of treatment. These promising data justify further evaluation of the mechanism and role of fenofibrate, in addition to standard therapy, in the management of diabetic retinopathy.


2020 ◽  
Vol 8 (2) ◽  
pp. e001710
Author(s):  
Byung Joo Lee ◽  
Hye Eun Byeon ◽  
Chang Sik Cho ◽  
Young Ho Kim ◽  
Jin Hyoung Kim ◽  
...  

IntroductionSystemic histaminergic activity is elevated in patients with diabetes mellitus. There are a few studies suggesting that histamine is implicated in the pathogenesis of diabetes, but the exact role of histamine in the development of diabetic retinopathy is unclear. The aim of this study was to investigate the role of histamine receptor H4 (HRH4) in the regulation of retinal pigment epithelium (RPE)-derived pro-angiogenic and anti-angiogenic factors under diabetic conditions.Research design and methodsThe levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), histamine and histidine decarboxylase (HDC) in the serum and vitreous samples of patients with diabetes were compared with those of patients without diabetes. The effect of hyperglycemia on expression levels of HRH4, VEGF, IL-6 and pigment epithelium-derived factor (PEDF) in the RPE was determined. The role of HRH4 in high glucose-induced regulation of VEGF, IL-6 and PEDF in ARPE-19 cells and the underlying regulatory mechanism were verified using an RNA interference-mediated knockdown study.ResultsThe serum and vitreous levels of VEGF, IL-6, histamine and HDC were more increased in patients with diabetic retinopathy than in patients without diabetes. HRH4 was overexpressed in RPE both in vitro and in vivo. Histamine treatment upregulated VEGF and IL-6 and downregulated PEDF expression in ARPE-19 cells cultivated under hyperglycemic conditions. Hyperglycemia-induced phosphorylation of p38 and subsequent upregulation of VEGF and IL-6 and downregulation of PEDF were dampened by small interfering RNA-mediated knockdown of HRH4 in ARPE-19 cells.ConclusionsTaken together, HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.


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