Recent advances in the management of diabetic retinopathy

Dulull, Nabeela K.; Kwa, Faith A.A.; Osman, Narin; Rai, Uma; Shaikh, Bilal; Thrimawithana, Thilini

doi:10.1016/j.drudis.2019.03.028

Cited by 21 publications

(21 citation statements)

References 93 publications

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“…Further, VEGF-A 165 is a potent mitogen for endothelial cells triggering their proliferation, migration and tube formation resulting in the growth of new blood vessels along the inside surface of the retina and in the vitreous that, however, in the diabetic retina are fragile and may break (Antonetti et al, 2012). In turn, these events may entail vitreous hemorrhage, subsequent fibrosis, and tractional retinal detachment with risk of permanent vision loss in the affected eye (Dulull et al, 2019). Hence, due to this dual capability to promote both vascular permeability and pathologic angiogenic proliferation, VEGF-A constitutes a key player in DR and therefore a compelling druggable target (Amadio et al, 2016a;Zhao and Singh, 2018).…”

Section: Introductionmentioning

confidence: 99%

Short-and Long-Term Expression of Vegf: A Temporal Regulation of a Key Factor in Diabetic Retinopathy

et al. 2021

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To investigate the role of vascular endothelial growth factor (VEGF) at different phases of diabetic retinopathy (DR), we assessed the retinal protein expression of VEGF-A164 (corresponding to the VEGF165 isoform present in humans, which is the predominant member implicated in vascular hyperpermeability and proliferation), HIF-1α and PKCβ/HuR pathway in Ins2Akita (diabetic) mice at different ages. We used C57BL6J mice (WT) at different ages as control. Retina status, in terms of tissue morphology and neovascularization, was monitored in vivo at different time points by optical coherence tomography (OCT) and fluorescein angiography (FA), respectively. The results showed that VEGF-A164 protein expression increased along time to become significantly elevated (p < 0.05) at 9 and 46 weeks of age compared to WT mice. The HIF-1α protein level was significantly (p < 0.05) increased at 9 weeks of age, while PKCβII and HuR protein levels were increased at 46 weeks of age compared to WT mice. The thickness of retinal nerve fiber layer as measured by OCT was decreased in Ins2Akita mice at 9 and 46 weeks of age, while no difference in the retinal vasculature were observed by FA. The present findings show that the retina of the diabetic Ins2Akita mice, as expected for mice, does not develop proliferative retinopathy even after 46 weeks. However, diabetic Ins2Akita mice recapitulate the same evolution of patients with DR in terms of both retinal neurodegeneration and pro-angiogenic shift, this latter indicated by the progressive protein expression of the pro-angiogenic isoform VEGF-A164, which can be sustained by the PKCβII/HuR pathway acting at post-transcriptional level. In agreement with this last concept, this rise in VEGF-A164 protein is not paralleled by an increment of the corresponding transcript. Nevertheless, the observed increase in HIF-1α at 9 weeks indicates that this transcription factor may favor, in the early phase of the disease, the transcription of other isoforms, possibly neuroprotective, in the attempt to counteract the neurodegenerative effects of VEGF-A164. The time-dependent VEGF-A164 expression in the retina of diabetic Ins2Akita mice suggests that pharmacological intervention in DR might be chosen, among other reasons, on the basis of the specific stages of the pathology in order to pursue the best clinical outcome.

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Section: Introductionmentioning

confidence: 99%

Short-and Long-Term Expression of Vegf: A Temporal Regulation of a Key Factor in Diabetic Retinopathy

et al. 2021

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“…To a certain extent, the onset of DR relies on the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries[ 35 ]. Moreover, accumulating evidence has shown that treatments to inhibit the inflammatory reaction, such as intravitreal steroids, interleukin-6 (IL-6) inhibitors, IL-6 receptor inhibitors, and integrin inhibitors, are effective in preventing the development and worsening of DR[ 6 , 23 ].…”

Section: Inflammation In Dr Pathogenesismentioning

confidence: 99%

“…Diabetic retinopathy (DR) has been recognized as a neurovasculopathy of diabetes and is a leading cause of blindness in populations of 20-74 years old in many developed countries[ 2 - 4 ], accounting for 2.6% of blinding cases around the world[ 5 ]. Nearly 30% of diabetic patients develop into DR[ 6 ], and once the course of diabetes extends beyond 15 years, DR can occur in almost 98% of patients with type 1 diabetes (T1D) and more than 80% of patients with type 2 diabetes (T2D)[ 7 ]. Similarly, the chance of developing sight-threatening DR is higher in T1D patients (11%) than in T2D patients (3%)[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Role of interferons in diabetic retinopathy

Li¹,

Tan²,

Zou³

et al. 2021

WJD

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Diabetic retinopathy (DR) is one of the major causes of visual impairment and irreversible blindness in developed regions. Aside from abnormal angiogenesis, inflammation is the most specific and might be the initiating factor of DR. As a key participant in inflammation, interferon-gamma (IFN-γ) can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines, which accelerate neovascularization and neuroglial degeneration. In addition, IFN-γ is involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases, such as diabetic nephropathy, cerebral microbleeds, and age-related macular degeneration. Traditional treatments, such as anti-vascular endothelial growth factor agents, vitrectomy, and laser photocoagulation therapy, are more effective for angiogenesis and not tolerable for every patient. Many ongoing clinical trials are exploring effective drugs that target inflammation. For instance, IFN-α acts against viruses and angiogenesis and is commonly used to treat malignant tumors. Moreover, IFN-α has been shown to contribute to alleviating the progression of DR and other ocular diseases. In this review, we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR, such as diagnosis, prognosis, and therapeutic treatment.

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“…In this environment, severe diseases can easily develop. High levels of advanced glycation-end products (AGEs), such as glycated haemoglobin (HbA1c) and glycated albumin (GA) [99], are responsible for endothelial and vascular dysfunction, prolonged inflammation [100], bone damages [101] and fragility [102] and impaired functions in the peripheral nerves [103]. Vascular and endothelial abnormalities causes atherosclerosis and thrombosis [104], neuropathy and retinopathy [105].…”

Section: Diabetes Pathophysiology and Epidemiologymentioning

confidence: 99%