Emerging Insights and Interventions for Diabetic Retinopathy

Honasoge, Avinash; Nudleman, Eric; Smith, Morton E.; Rajagopal, Rithwick

doi:10.1007/s11892-019-1218-2

Cited by 29 publications

(13 citation statements)

References 153 publications

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“…Diabetic retinopathy (DR) is a common complication associated with diabetic macular edema, vitreous hemorrhage, traction retinal detachment, and macular ischemia [ 14 ]. Although DR progression leads to vision loss, only limited effective treatments are currently available.…”

Section: Introductionmentioning

confidence: 99%

Axon guidance molecules in immunometabolic diseases

2022

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The global prevalence of metabolic diseases, such as obesity, diabetes, and atherosclerosis, is rapidly increasing and has now reached epidemic proportions. Chronic tissue inflammation is a characteristic of these metabolic diseases, indicating that immune responses are closely involved in the pathogenesis of metabolic disorders. However, the regulatory mechanisms underlying immunometabolic crosstalk in these diseases are not completely understood. Recent studies have revealed the multifaceted functions of semaphorins, originally identified as axon guidance molecules, in regulating tissue inflammation and metabolic disorders, thereby highlighting the functional coupling between semaphorin signaling and immunometabolism. In this review, we explore how semaphorin signaling transcends beyond merely guiding axons to controlling immune responses and metabolic diseases.

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Section: Introductionmentioning

confidence: 99%

Axon guidance molecules in immunometabolic diseases

2022

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“…Vision loss from DR commonly occurs because of a progressive vasculopathy that has well-defined ophthalmoscopic characteristics ( 28 ). However, damage to the retina in diabetes occurs long before the onset of such lesions and likely involves numerous nonvascular cell types of the retina, notably photoreceptors.…”

Section: Discussionmentioning

confidence: 99%

Glucose-mediated de novo lipogenesis in photoreceptors drives early diabetic retinopathy

Rajagopal

Sylvester

Zhang

et al. 2021

Journal of Biological Chemistry

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Diabetic retinopathy (DR) is an increasingly frequent cause of blindness across populations; however, the events that initiate pathophysiology of DR remain elusive. Strong preclinical and clinical evidence suggests that abnormalities in retinal lipid metabolism caused by diabetes may account for the origin of this disease. A major arm of lipid metabolism, de novo biosynthesis, is driven by elevation in available glucose, a common thread binding all forms of vision loss in diabetes. Therefore, we hypothesized that aberrant retinal lipid biogenesis is an important promoter of early DR. In murine models, we observed elevations of diabetes-associated retinal de novo lipogenesis ∼70% over control levels. This shift was primarily because of activation of fatty acid synthase (FAS), a rate-limiting enzyme in the biogenic pathway. Activation of FAS was driven by canonical glucose-mediated disinhibition of acetyl-CoA carboxylase, a major upstream regulatory enzyme. Mutant mice expressing gain-of-function FAS demonstrated increased vulnerability to DR, whereas those with FAS deletion in rod photoreceptors maintained preserved visual responses upon induction of diabetes. Excess retinal de novo lipogenesis—either because of diabetes or because of FAS gain of function—was associated with modestly increased levels of palmitate-containing phosphatidylcholine species in synaptic membranes, a finding with as yet uncertain significance. These findings implicate glucose-dependent increases in photoreceptor de novo lipogenesis in the early pathogenesis of DR, although the mechanism of deleterious action of this pathway remains unclear.

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“…Future Perspectives. Different adjuvant therapies have been evaluated in this review focusing mainly on diminishing the progression of DR, through other routes, such as using light stimulation or pharmacological strategies to shift photoreceptors into less energy-consuming metabolic states [247]. The complexity to deliver cost-effective drugs to the posterior segment of the eye has led to novel approaches [248].…”

Section: Designmentioning

confidence: 99%

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation

Robles-Rivera

Castellanos-González

Olvera-Montaño

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diabetes mellitus (DM) is a progressive disease induced by a sustained state of chronic hyperglycemia that can lead to several complications targeting highly metabolic cells. Diabetic retinopathy (DR) is a multifactorial microvascular complication of DM, with high prevalence, which can ultimately lead to visual impairment. The genesis of DR involves a complex variety of pathways such as oxidative stress, inflammation, apoptosis, neurodegeneration, angiogenesis, lipid peroxidation, and endoplasmic reticulum (ER) stress, each possessing potential therapeutic biomarkers. A specific treatment has yet to be developed for early stages of DR since no management is given other than glycemic control until the proliferative stage develops, offering a poor visual prognosis to the patient. In this narrative review article, we evaluate different dietary regimens, such as the Mediterranean diet, Dietary Pattern to Stop Hypertension (DASH) and their functional foods, and low-calorie diets (LCDs). Nutraceuticals have also been assessed in DR on account of their antioxidant, anti-inflammatory, and antiangiogenic properties, which may have an important impact on the physiopathology of DR. These nutraceuticals have shown to lower reactive oxygen species (ROS), important inflammatory factors, cytokines, and endothelial damage biomarkers either as monotherapies or combined therapies or concomitantly with established diabetes management or nonconventional adjuvant drugs like topical nonsteroidal anti-inflammatory drugs (NSAIDs).

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Emerging Insights and Interventions for Diabetic Retinopathy

Cited by 29 publications

References 153 publications

Axon guidance molecules in immunometabolic diseases

Axon guidance molecules in immunometabolic diseases

Glucose-mediated de novo lipogenesis in photoreceptors drives early diabetic retinopathy

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation

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