A Paradigm Shift in the Management Approaches of Proliferative Diabetic Retinopathy: Role of Anti-VEGF Therapy

Raman, Rajiv; Ramasamy, Kim; Shah, Utkarsh

doi:10.2147/opth.s374165

Cited by 4 publications

(3 citation statements)

References 93 publications

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“…Since the late 20th, laser photocoagulation was used to destroy the part of the retina that lacks oxygen in order to avoid neovessel proliferation and to prevent hemorrhages in the vitreous, while vitrectomy was applied when blood extravasation affects visual acuity ( Oellers and Mahmoud, 2016 ; Zhang et al, 2023 ). In this respect, panretinal photocoagulation is still the main treatment for PDR, allowing the regression of retinal and papillary new vessels ( Raman et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

Cammalleri,

Filippi,

Dal Monte

et al. 2024

Front. Physiol.

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Although compartmentalization of the eye seems to promote its experimental manipulation, drug penetration to its posterior part is severely limited by hard barriers thus hindering drug development for eye diseases. In particular, angiogenesis-related retinal diseases share common mechanisms and are responsible for the majority of cases of blindness. Their prevalence is globally increasing mostly because of the increased incidence of systemic pathologies in the adult. Despite the number of preclinical findings demonstrating the efficacy of novel treatments, therapy of retinal neovascular diseases still remains confined to intravitreal anti-vascular endothelial growth factor treatments with some extension to anti-inflammatory therapy. In the mare magnum of preclinical findings aimed to develop novel avenues for future therapies, most compounds, despite their efficacy in experimental models, do not seem to meet the criteria for their therapeutic application. In particular, the groove between preclinical findings and their clinical application increases instead of decreasing and the attempt to bridging the gap between them creates intense frustration and a sense of defeat. In this complex scenario, we will discuss here the role that overactivation of the sympathetic system plays in retinal vessel proliferation in response to hypoxia using the oxygen-induced retinopathy (OIR) model. The potential application of the beta-adrenoceptor (β-AR) blockade with propranolol to the treatment of retinopathy of prematurity will be also discussed in light of preclinical findings in the OIR model and clinical trials using propranolol in preterm infants either per os or as eye drops.

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Section: Introductionmentioning

confidence: 99%

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

Cammalleri,

Filippi,

Dal Monte

et al. 2024

Front. Physiol.

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“…The current therapeutic approaches for PDR mainly involve laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. However, these therapeutic modalities do not always effectively control the progression of PDR 5 . Moreover, studies have indicated that initiating intravitreal anti-VEGF medication increases the risk of acute thromboembolic events, particularly ischemic strokes 6 .…”

Section: Introductionmentioning

confidence: 99%

The Warburg effect alters amino acid homeostasis in human retinal endothelial cells: implication for proliferative diabetic retinopathy

Gregory,

Yumnamcha,

Shawky

et al. 2023

Sci Rep

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Proliferative diabetic retinopathy (PDR) remains a leading cause of blindness despite progress in screening and treatment. Recently, the Warburg effect, a metabolic alteration affecting amino acid (AA) metabolism in proliferating cells, has drawn attention regarding its role in PDR. This study aimed to investigate the impact of the Warburg effect on AA metabolism in human retinal endothelial cells (HRECs) subjected to PDR-associated risk factors and validate the findings in patients with PDR. In vitro experiments exposed HRECs to high glucose (HG) and/or hypoxia (Hyp), known inducers of the Warburg effect. The HG + Hyp group of HRECs exhibited significant differences in non-essential AAs with aliphatic non-polar side chains, mainly driven by elevated glycine concentrations. Pathway enrichment analysis revealed several glycine metabolism-related pathways significantly altered due to the Warburg effect induced by HG + Hyp. Crucially, vitreous humor samples from PDR patients displayed higher glycine levels compared to non-diabetic and diabetic patients without PDR. The odds ratio for PDR patients with glycine levels above the cut-off of 0.0836 µM was 28 (p = 0.03) compared to non-PDR controls. In conclusion, this study provides mechanistic insights into how a specific Warburg effect subtype contributes to glycine accumulation in PDR and supports glycine's potential as a biomarker for PDR pathogenesis.

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“…While angiogenesis is defective in cardiac microvessels in DM, it is pathologically enhanced in the retina. Overactive VEGF signaling and increased vascular permeability are involved in the pathogenesis of diabetic retinopathy [273]. Herein, miRNA expression profiling from STZ-mice informed on the downregulation of miR-200b.…”

Section: Mirnas In Pathogenesis and Potential Therapy Of Dm And Cvdmentioning

confidence: 99%

Cardiac microvascular dysfunction in diabetes mellitus: elucidation of molecular determinants and therapeutic targets

Samak¹

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gezeigt, dass die Hemmung von miR-92a die Werte dieser Targets in diabetischen HCMEC wiederherstellt. Insgesamt zeigen meine Ergebnisse neue molekulare Mechanismen in derPathogenese der kardialen mikrovaskulären Dysfunktion bei Diabetes mellitus auf und qualifizieren miR-92a nachdrücklich als therapeutisches Ziel. Type 1 diabetes mellitus (T1DM)Type 1 DM is a chronic autoimmune disease characterized by progressive destruction of the pancreatic insulin producing beta cells (β-cells) in the islets of Langerhans by cytotoxic T-cells, resulting in insulin deficiency and hyperglycemia [10]. T1DM is a polygenic disease, wherein various susceptibility genes, along with precipitating environmental and/or infectious agents trigger an overt immune reaction to β-cells [11]. As a result, the endocrine pancreas is infiltrated with cytotoxic CD8+ T-cells along with cells of the innate immune system, as well as B-lymphocytes [10][11]. The latter release autoantibodies against β-cell proteins, which are characteristic measures in the blood of T1DM patients [10]. The disease usually presents itself in children or young individuals, hence previously known as juvenile-onset DM. This can be misleading, since T1DM can occur in any age, with 50% of cases occurring in adults, of which half are misdiagnosed as type 2 DM [12][13]. T1DM affects one in every 250 individuals on average, with more male than female bias [14]. The incidence of T1DM has been on the rise, with overall annual increase of 2 -3%, mostly children under 15 years old, peaking at those < 5 years old [15]. Type 1 diabetic patients are strictly dependent on exogenous insulin with high risk of life-threatening bouts of hypoglycemia, and on the other end, diabetic ketoacidosis [10].These critical conditions have been associated with neurocognitive complications in type 1 diabetic patients, which are linked to diabetes-induced vascular disease [16][17][18]. Type 1 diabetics succumb to the notorious long-term complications of DM, including retinopathy, nephropathy and neuropathy, and above all cardiovascular disease (CVD) (discussed below) [19][20][21][22]. Despite recent improvements in management, T1DM continues to be associated with increased total mortality. In young adults with T1DM, i.e. <45 years old, total mortality is 5 fold higher than among age-matched non-diabetics [23]. pancreatic compensation fails in face of insulin resistance, leading to β-cell dysfunction [26][27]. The triad of increased blood glucose, insulin and free fatty acids is an ominous metabolic state that evoke a number of deleterious cascades, such as glucotoxicity, lipotoxicity, oxidative stress, dyslipidemia and inflammation, that inflict all organ systems [28][29]. These manifest in a wide range of diabetic infamous complications, such as retinopathy, neuropathy, nephropathy and above all, CVD (discussed below) [26]. Importantly, T2DM harbors a genetic component that has recently become appreciated thanks to advancing genome wide association studies (GWAS). Over 500 risk variants and susceptibi...

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A Paradigm Shift in the Management Approaches of Proliferative Diabetic Retinopathy: Role of Anti-VEGF Therapy

Cited by 4 publications

References 93 publications

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

The Warburg effect alters amino acid homeostasis in human retinal endothelial cells: implication for proliferative diabetic retinopathy

Cardiac microvascular dysfunction in diabetes mellitus: elucidation of molecular determinants and therapeutic targets

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