Diabetic retinal neurodegeneration as a form of diabetic retinopathy

Soni, Deepak; Sagar, Pradeep; Takkar, Brijesh

doi:10.1007/s10792-021-01864-4

Cited by 39 publications

(29 citation statements)

References 190 publications

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“…This phenomenon suggested that the swelling of the GCL axon preceded the GCL cell body loss under hyperglycemia, thereby reflecting the unique hypoglycemia-mediated pathological damage of GCL. The pathological evidence, either in animal models or humans, is consistent with the findings of the current study (53)(54)(55)(56)(57). Furthermore, FAZp, FAZ-CI, and VD are good sensors of retinal ischemia and have been implicated in several clinical studies to predict disease progression (58)(59)(60).…”

Section: Discussionsupporting

confidence: 89%

“…A total of 76 patients (76 eyes) with type 2 diabetes mellitus (T2DM) were enrolled in this study, including 39 males and 37 females, aged 40-71 years (average 58.34 ± 7.47 years), with a refractive error between −3.0 diopter (D) and +3.0 D and registered in the outpatient clinic of Beijing Tongren Hospital from September 2018 to September 2019. Age-, sex-, and refractive error-matched 28 healthy subjects (28 eyes) [aged 43-78 years, median (interquartile, IQR) 53 (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62) years] constituted the normal control group. If bilateral eyes were diagnosed as DR in patients with T2DM, only the severely affected eye was enrolled in the study.…”

Section: Participantsmentioning

confidence: 99%

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Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography

et al. 2021

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Purpose: To provide clinical evidence of the associations between retinal neuronal degeneration and microvasculopathy in diabetic retinopathy (DR).Methods: This case-control study included 76 patients (76 eyes) with type 2 diabetes mellitus (DM), and refraction error between −3.0 and +3.0 D. The eyes were assigned into DM (without DR), non-proliferative DR (NPDR), and proliferative DR (PDR) groups. Age-, sex-, and refractive error-matched normal subjects were enrolled as controls. The mean retinal thickness (mRT), the relative mean thickness of the retinal nerve fiber layer (rmtRNFL, mtRNFL/mRT), ganglion cell layer (rmtGCL), ganglion cell complex (rmtGCC) layer, foveal avascular zone area (FAZa), FAZ perimeter (FAZp), FAZ circularity index (FAZ-CI), and vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Group comparison and Spearman's partial correlation coefficient analysis were applied to evaluate the correlation between these morphological parameters.Results: rmtRNFL, FAZa, and FAZp in SCP and DCP increased with the DR severity (prmtRNFL < 0.001; pFAZa, SCP = 0.001; pFAZa, DCP = 0.005; pFAZp, SCP < 0.001; pFAZp, DCP < 0.001). The rmtGCL, FAZ-CI in SCP and DCP, and VD in DCP decreased with the DR severity (prmtGCL = 0.002, pFAZ−CI, SCP = 0.002; pFAZ−CI, DCP < 0.001, pVD, DCP < 0.001). After controlling age, sex, duration of diabetes, and hypertension, the rmtRNFL, FAZa in SCP and DCP, and FAZp in SCP and DCP were correlated with the severity of DR (p < 0.05), while VD in SCP and DCP, FAZ-CI, and rmtGCL were negatively correlated with the severity of DR (p < 0.05). The rmtGCL was negatively correlated with the FAZa in SCP (r = −0.34, p = 0.002) and DCP (r = −0.23, p = 0.033), and FAZp in SCP (r = −0.37, p = 0.001) and DCP (r = −0.32, p = 0.003), but positively correlated with VD in SCP (r = 0.26, p = 0.016), VD in DCP (r = 0.28, p = 0.012), and FAZ-CI in DCP (r = 0.31, p = 0.006).Conclusions: rmtRNFL, FAZ-CI in SCP and DCP, and FAZp in SCP are strong predictors of the severity of DR. The ganglion cell body loss is highly correlated with increased FAZp and FAZa, decreased FAZ-CI, and reduced VD with the severity of DR.

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Section: Discussionsupporting

confidence: 89%

Section: Participantsmentioning

confidence: 99%

Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography

et al. 2021

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“…Diabetic retinopathy remains a major cause of vision loss in the working-age population of Western countries, andthe incidence may increase due to the increased prevalence of diabetes worldwide [1]. Indeed, despite the widespread use of intraocular anti-VEGF Pharmaceutics 2021, 13, 1095 2 of 16 drugs and glucocorticoids, mainly designed to act on macular edema, visual function is threatened by ischemic insults and by direct diabetic-induced neuropathy [2,3]. The neuropathy occurs early, even before microangiopathy is detected, as shown by recent retinal imaging technologies [3] or by electrophysiology showing progressive deterioration of electrical retinal responses with loss of electrical signal amplitudes and extended response times, reflecting retinal neuron alterations [4,5].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model

et al. 2021

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Diabetic retinopathy (DR) remains a major cause of vision loss, due to macular edema, retinal ischemia and death of retinal neurons. We previously demonstrated that acute administration of glibenclamide into the vitreous, or given orally at a non-hypoglycemic dose, protected the structure and the function of the retina in three animal models that each mimic aspects of diabetic retinopathy in humans. In this pilot study, we investigated whether one year of chronic oral glibenclamide, in a non-hypoglycemic regimen (Amglidia®, 0.4 mg/kg, Ammtek/Nordic Pharma, 5 d/week), could alleviate the retinopathy that develops in the Goto-Kakizaki (GK) rat. In vivo, retinal function was assessed by electroretinography (ERG), retinal thickness by optical coherence tomography (OCT) and retinal perfusion by fluorescein and indocyanin green angiographies. The integrity of the retinal pigment epithelium (RPE) that constitutes the outer retinal barrier was evaluated by quantitative analysis of the RPE morphology on flat-mounted fundus ex vivo. Oral glibenclamide did not significantly reduce the Hb1Ac levels but still improved retinal function, as witnessed by the reduction in scotopic implicit times, limited diabetes-induced neuroretinal thickening and the extension of ischemic areas, and it improved the capillary coverage. These results indicate that low doses of oral glibenclamide could still be beneficial for the prevention of type 2 diabetic retinopathy. Whether the retinas ofpatients treated specifically with glibenclamideare less at risk of developing diabetic complications remains to be demonstrated.

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“…Trials conducted in the last century had contrasting results. The Dipyridamole Aspirin Microangiography of Diabetes Study Group (DAMAD) showed a small reduction in the number of microaneurysms (MAs) in an aspirin = treated group whereas the Early Treatment of Diabetic Retinopathy Research Group (ETDRS) found no significant difference in the impact of aspirin on DR.[ 172 173 ] the current research has shown promising pre-clinical results with many anti-inflammatory agents in their domains, and in the future, we are likely to see a higher level of evidence as clinical trials unfold. While steroids as broad-spectrum agents have been tested extensively for DR and DME, risuteganib is a prime example of a possible targeted therapy acing at the level of integrins and is entering phase 3 trials.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory mediators in diabetic retinopathy: Deriving clinicopathological correlations for potential targeted therapy

Sheemar

Soni

Takkar

et al. 2021

Indian Journal of Ophthalmology

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The role of inflammation in diabetic retinopathy (DR) is well-established and dysregulation of a large number of inflammatory mediators is known. These include cytokines, chemokines, growth factors, mediators of proteogenesis, and pro-apoptotic molecules. This para-inflammation as a response is not directed to a particular pathogen or antigen but is rather directed toward the by-products of the diabetic milieu. The inflammatory mediators take part in cascades that result in cellular level responses like neurodegeneration, pericyte loss, leakage, capillary drop out, neovascularization, etc. There are multiple overlaps between the inflammatory pathways occurring within the diabetic retina due to a large number of mediators, their varied sources, and cross-interactions. This makes understanding the role of inflammation in clinical manifestations of DR difficult. Currently, mediator-based therapy for DR is being evaluated for interventions that target a specific step of the inflammatory cascade. We reviewed the role of inflammation in DR and derived a simplified clinicopathological correlation between the sources and stimuli of inflammation, the inflammatory mediators and pathways, and the clinical manifestations of DR. By doing so, we deliberate mediator-specific therapy for DR. The cross-interactions between inflammatory mediators and the molecular cycles influencing the inflammatory cascades are crucial challenges to such an approach. Future research should be directed to assess the feasibility of the pathology-based therapy for DR.

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Diabetic retinal neurodegeneration as a form of diabetic retinopathy

Cited by 39 publications

References 190 publications

Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography

Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography

Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model

Inflammatory mediators in diabetic retinopathy: Deriving clinicopathological correlations for potential targeted therapy

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