Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

Özdemir, Gökhan; Kılınç, Metin; Ergün, Yusuf; Şahin, Elif

doi:10.1016/j.jcjo.2014.07.003

Cited by 21 publications

(12 citation statements)

References 44 publications

(77 reference statements)

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“…However, another study showed an increase in LC3B-II after 24 h of ischemia 24 . Rapamycin induction of autophagy in diabetic retinopathy, which results in chronic ischemic changes in the retina, angiogenesis, decreases vascular endothelial growth factor production, and suppresses retinal oxidative stress 31 , 32 . Ischemia to the retina induces glucose deprivation or oxidative stress, and AMPK plays a pivotal role in energy homeostasis and metabolism under these conditions 33 .…”

Section: Discussionmentioning

confidence: 99%

Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas

Park

Kim

2018

Sci Rep

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Diabetes mellitus and glaucoma are the two major causes of selective retinal ganglion cell (RGC) death. To determine the relationship between autophagy and RGC death, we compared autophagy and the related molecular pathways in diabetic and glaucomatous retinas and examined their effect on RGC survival. Biochemical analysis of microtubule-associated protein light chain 3 (LC3)-II and beclin-1 were observed. To determine the pathways involved in autophagy induction, adenosine monophosphate-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR) were also explored. Beclin-1 and the LC3B-II to LC3B-I ratio significantly elevated at 4 and 8 weeks after glaucoma induction; however, only a slight increase was apparent in the diabetic retina. Significant upregulation of phosphorylated AMPK and downregulation of phosphorylated mTOR was evident in the diabetic retina. After autophagy was inhibited with 3-methyladenine (3-MA), apoptosis of RGCs was significantly increased in the diabetic retinas. However, 3-MA inhibition of autophagy decreased the apoptosis of RGCs in glaucomatous retinas. Therefore, our results suggest that RGC death is differentially regulated by autophagy and that the pathways involved differ depending on the triggering injury.

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Section: Discussionmentioning

confidence: 99%

Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas

Park

Kim

2018

Sci Rep

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“…A recent study further suggests a strong correlation between the serum levels of HIF-1a in patients and development of DR (Sayed & Mahmoud 2016). Besides HIF-1a inducing VEGF transcription, other factors such as oxidative stress and pro-inflammatory cytokines (PICs) are involved in DR development (Gustavsson et al 2008;Wang et al 2008;Wilkinson-Berka et al 2013;Ozdemir et al 2014). It has been reported that PICs including IL1b, IL-6 and TNF-a in retinal tissues of DR are increased in animals and patients with DR, which is consistent with a role for PICs in engagement of the pathophysiology of DR (Mocan et al 2006;Gustavsson et al 2008).…”

Section: Introductionmentioning

confidence: 98%

Inhibition of HIF‐1α decreases expression of pro‐inflammatory IL‐6 and TNF‐α in diabetic retinopathy

Gao

Wang

et al. 2016

Acta Ophthalmologica

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“…Among these are drugs targeting a central regulator, such as Raf kinase, mammalian target of rapamycin (mTOR) and the RTP 801 gene. [274][275][276] A Phase I/II study of an ankyrin repeat protein that binds VEGF reduced DME when injected intravitreally in several patients with a duration of effect of 8-12 weeks but had a tendency to cause iritis. 277 A modified version designed to eliminate the problem of iritis is undergoing further clinical testing.…”

Section: Future Trends Diagnosticsmentioning

confidence: 99%

<p>The Evolving Treatment of Diabetic Retinopathy</p>

Mansour¹,

Browning²,

Wong³

et al. 2020

OPTH

162

119

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Purpose: To review the current therapeutic options for the management of diabetic retinopathy (DR) and diabetic macular edema (DME) and examine the evidence for integration of laser and pharmacotherapy. Methods: A review of the PubMed database was performed using the search terms diabetic retinopathy, diabetic macular edema, neovascularization, laser photocoagulation, intravitreal injection, vascular endothelial growth factor (VEGF), vitrectomy, pars plana vitreous surgery, antiangiogenic therapy. With additional cross-referencing, this yielded 835 publications of which 301 were selected based on content and relevance. Results: Many recent studies have evaluated the pharmacological, laser and surgical therapeutic strategies for the treatment and prevention of DR and DME. Several newer diagnostic systems such as optical coherence tomography (OCT), microperimetry, and multifocal electroretinography (mfERG) are also assisting in further refinements in the staging and classification of DR and DME. Pharmacological therapies for both DR and DME include both systemic and ocular agents. Systemic agents that promote intensive glycemic control, control of dyslipidemia and antagonists of the renin-angiotensin system demonstrate beneficial effects for both DR and DME. Ocular therapies include anti-VEGF agents, corticosteroids and nonsteroidal anti-inflammatory drugs. Laser therapy, both as panretinal and focal or grid applications continue to be employed in management of DR and DME. Refinements in laser devices have yielded more tissue-sparing (subthreshold) modes in which many of the benefits of conventional continuous wave (CW) lasers can be obtained without the adverse side effects. Recent attempts to lessen the burden of anti-VEGF injections by integrating laser therapy have met with mixed results. Increasingly, vitreoretinal surgical techniques are employed for less advanced stages of DR and DME. The development and use of smaller gauge instrumentation and advanced anesthesia agents have been associated with a trend toward earlier surgical intervention for diabetic retinopathy. Several novel drug delivery strategies are currently being examined with the goal of decreasing the therapeutic burden of monthly intravitreal injections. These fall into one of the five categories: non-biodegradable polymeric drug delivery systems, biodegradable polymeric drug delivery systems, nanoparticle-based drug delivery systems, ocular injection devices and with sustained release refillable devices. At present, there remains no one single strategy for the management of the particular stages of DR and DME as there are many options that have not been rigorously tested through large, randomized, controlled clinical trials. Conclusion: Pharmacotherapy, both ocular and systemic, will be the primary mode of intervention in the management of DR and DME in many cases when cost and treatment burden are less constrained. Conventional laser therapy has become a secondary intervention in these instances, but remains a first-line option when cost and ...

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Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

Cited by 21 publications

References 44 publications

Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas

Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas

Inhibition of HIF‐1α decreases expression of pro‐inflammatory IL‐6 and TNF‐α in diabetic retinopathy

<p>The Evolving Treatment of Diabetic Retinopathy</p>

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