Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes

Campos, António; Martins, João; Campos, Elisa J.; Silva, Rufino; Ambrósio, António Francisco

doi:10.1016/j.biopha.2020.110811

Cited by 13 publications

(6 citation statements)

References 63 publications

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“…In vivo study on GK rats (a rat model of Type 2 diabetes) showed that, the VD of CC was reduced. This finding is consistent with the CC degeneration found in humans with T2D, either by post-mortem or OCT-angiography (OCTA) specimens [52][53][54].…”

Section: Vd In CCsupporting

confidence: 89%

Quantitative assessment of vascular density in diabetic retinopathy subtypes with optical coherence tomography angiography

et al. 2021

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Background Quantitative assessment of vascular density (VD) of retinal and choriocapillaris (CC) in various stages of diabetic retinopathy (DR) using spectral domain optical coherence tomography angiography (SD OCTA). Methods 188 eyes of 97 participants were recruited in this cross-sectional study. The macular OCTA (3x3mm) scan was performed and the computer algorithm assessed VD at the level of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC. Results All measured parameters were decreased in retinal VD at the more extreme stages of DR, with the exception of SCP foveal VD. There was a constant pattern of decrease in VD of CC from normal cases to cases of NDR and NPDR and then a slight increase occurred in the PDR stage but never touching the normal quantities. Age, fasting blood sugar, and years of diabetes mellitus were correlated with reduced VD in different segments. Multivariate linear regression analysis showed that best-corrected visual acuity (BCVA) was positively correlated with parafoveal VD at SCP and VD of foveal area at CC. VD of all subfields of macular area except foveal DCP VD showed reduced levels in diabetic macular edema (DME) patients compared to those without DME. Conclusions The findings of the study endorse retina VD changes as a potential biomarker for DR development before retinopathy becomes clinically evident. It seems that parafoveal VD of SCP and foveal VD of CC are good biomarkers to predict VA in the diabetic patients.

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Section: Vd In CCsupporting

confidence: 89%

Quantitative assessment of vascular density in diabetic retinopathy subtypes with optical coherence tomography angiography

et al. 2021

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“…Male GK rats develop late complications such as microangiopathy, nephropathy, neuropathy and retinopathy [ 25 ]. Although no animal model recapitulates all the features of human diabetic retinopathy, male GK rats develop progressive retinopathy with local inflammation, retinal circulatory abnormalities [ 26 ] and retinal edema [ 26 , 27 , 28 , 29 ], together with a thickening of the choroid [ 27 ], before microangiopathy develops at around 7 months [ 30 ], mimicking the kinetics of the events in human diabetic retina [ 31 ]. The retinopathy involves a PKCzetaoveractivation-linked blood–retinal barrier (BRB) breakdown, photoreceptor neurodegeneration [ 28 , 32 ], Müller cell swelling and morphological damage of the outer retina [ 21 ].…”

Section: Methodsmentioning

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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“…Recent studies conducted on T2DM animal models showed increased choroidal thickness with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina, and increased inflammatory cell density in the outer retina. 44 Differently, in T1DM animal models, no changes were demonstrated in choroidal thickness and choroidal vascular density during the early stages of the disease. 30 …”

Section: Inflammationmentioning

confidence: 93%

“…42,43 Recent studies conducted on T2DM animal models showed increased choroidal thickness with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina, and increased inflammatory cell density in the outer retina. 44 Differently, in T1DM animal models, no changes were demonstrated in choroidal thickness and choroidal vascular density during the early stages of the disease. 30 In vivo human studies, relying on optical coherence tomography (OCT), have revealed contradictory results regarding the choroidal thickness in different stages of DR. 45 Thus, the choroidal thickness is not yet a reliable parameter of diabetic choroidopathy in clinical practice.…”

Section: Rpe and Choroidmentioning

confidence: 93%

The role of inflammation and neurodegeneration in diabetic macular edema

et al. 2021

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The pathogenesis of diabetic macular edema (DME) is complex. Persistently high blood glucose activates multiple cellular pathways and induces inflammation, oxidation stress, and vascular dysfunction. Retinal ganglion cells, macroglial and microglial cells, endothelial cells, pericytes, and retinal pigment epithelium cells are involved. Neurodegeneration, characterized by dysfunction or apoptotic loss of retinal neurons, occurs early and independently from the vascular alterations. Despite the increasing knowledge on the pathways involved in DME, only limited therapeutic strategies are available. Besides antiangiogenic drugs and intravitreal corticosteroids, alternative therapeutic options tackling inflammation, oxidative stress, and neurodegeneration have been considered, but none of them has been currently approved.

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Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes

Cited by 13 publications

References 63 publications

Quantitative assessment of vascular density in diabetic retinopathy subtypes with optical coherence tomography angiography

Quantitative assessment of vascular density in diabetic retinopathy subtypes with optical coherence tomography angiography

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

The role of inflammation and neurodegeneration in diabetic macular edema

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