Correlation of Retinal Structure and Visual Function Assessments in Mouse Diabetes Models

Sheskey, Sarah; Antonetti, David A.; Renterı́a, René C.; Lin, Cheng‐mao

doi:10.1167/iovs.62.10.20

Cited by 23 publications

(10 citation statements)

References 36 publications

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“…Commonly used STZ-induced rodent models show the rapid onset of type 1 diabetes and several symptoms of DR. Loss of retinal pericytes and capillaries, thickening of the vascular basement membrane, and increased vascular permeability have been reported in STZ-induced rats [29,30]. In the present study, we found that the retinas tended to be thinner in STZ rats than in control rats, consistent with the previous study [31,23]. In our study, the model of DR rats was successfully established, as evidenced by the elevation of blood glucose concentration and decreased retina thickness.…”

Section: Discussionsupporting

confidence: 91%

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

Ouyang

Yuan

et al. 2023

Exp. Anim.

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Diabetic retinopathy (DR), a common complication of diabetes, involves excessive proliferation and inflammation of Muller cells and ultimately leads to vision loss and blindness. SRY-box transcription factor 9 (SOX9) has been reported to be highly expressed in Müller cells in retinal light-damaged rats, but the functional role of SOX9 in DR remains unclear. To explore this issue, the DR rat model was successfully constructed via injecting with streptozotocin (STZ, 65 mg/kg) and the retinal thicknesses and blood glucose levels were evaluated. Müller cells were treated with 25 mmol/L glucose to create a cell model in vitro. The results indicated that SOX9 expression was significantly increased in DR rat retinas and high glucose (HG)-stimulated Müller cells. HG treatment promoted the proliferation and migration capabilities of Müller cells, whereas SOX9 knockdown reversed those behaviors. Moreover, SOX9 knockdown protected against HG-induced inflammatory response, as evidenced by reduced tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels in serum and decreased NLRP3 inflammasome activation. Notably, SOX9, acted as a transcription factor that positively regulated thioredoxin-interacting protein (TXNIP), a positive regulator of Müller cells gliosis under HG conditions. Dual luciferase assay demonstrated that SOX9 could enhance TXNIP expression at the transcriptional level through binding to the promoter of TXNIP. Moreover, TXNIP overexpression restored the effects caused by SOX9 silencing. In conclusion, these findings demonstrate that SOX9 may accelerate the progression of DR by promoting glial cell proliferation, metastasis, and inflammation, which involves the transcriptional regulation of TXNIP, providing new theoretical fundamentals for DR therapy.

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Section: Discussionsupporting

confidence: 91%

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

Ouyang

Yuan

et al. 2023

Exp. Anim.

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“…As a result, peripheral retinal vessel whitening may be an indicator of reduced global retinal perfusion. Mouse models exhibited structural (retinal thinning) changes as well as functional (vision loss) as blood glucose levels increased 14 . Investigation of the macular retinal architecture and optical coherence tomography angiography among patients with peripheral retinal vessel whitening may provide insight into the process of microvascular changes and visual function.…”

Section: Discussionmentioning

confidence: 99%

Peripheral retinal vessel whitening in patients with diabetes mellitus

Kalaw,

Sharma,

Kako

et al. 2023

Sci Rep

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This study aimed to identify retinal vessel whitening outside the standard Early Treatment Diabetic Retinopathy Study (ETDRS) fields and to correlate the findings with vision and severity of diabetic retinopathy. Patients with diabetes mellitus who were seen in the retinal clinic to assess diabetic retinopathy status were included. Retinal vessel whitening was identified using ultra-widefield imaging. Four hundred and forty-five eyes of 260 patients were included. Thirty-five eyes in 24 patients (7.9%) were noted to have peripheral retinal vessel whitening. Thirty-one eyes with peripheral retinal vessel whitening did not have vessel whitening within the standard 7 ETDRS fields (p < 0.001). The proportion of whitening increased as DR severity increased, from 4.0% for patients with no DR (OR 0.249) to 33.3% for those with severe NPDR and PDR (OR 6.430 and 7.232, respectively). In addition, patients with peripheral retinal vessel whitening had worse visual acuity (logMAR = 0.34) compared to those without (logMAR = 0.15) (p < 0.001). In conclusion, we found an association between peripheral retinal vessel whitening in diabetic patients which correlated with diabetic retinopathy severity. Additionally, we found an association between vessel whitening and reduced vision, suggesting that vessel whitening identified using ultra-widefield imaging may be a prognostic indicator of vision in diabetic retinopathy.

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“…In addition to the development of insulin resistance causing chronic hyperglycemia, these mice also exhibit metabolic aberrations, including hypercholesterolemia, hypertriglyceridemia, and elevated free fatty acids, all of which mirror the macro- and microvascular complications seen in human T2DM patients [ 38 ]. The neurodegenerative aspects of human DR are recapitulated in the db/db mouse model and have previously been well characterized in male mice [ 20 , 39 , 40 ]. As early as 3 months of age, male db/db mice exhibit retinal thinning, decreased visual acuity, decreased scotopic a- and b-wave amplitude responses, and increased evidence of apoptosis in the inner retinal layers [ 20 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…The neurodegenerative aspects of human DR are recapitulated in the db/db mouse model and have previously been well characterized in male mice [ 20 , 39 , 40 ]. As early as 3 months of age, male db/db mice exhibit retinal thinning, decreased visual acuity, decreased scotopic a- and b-wave amplitude responses, and increased evidence of apoptosis in the inner retinal layers [ 20 , 39 , 40 ]. However, it has been recently reported that the prevalence of DR in T2DM patients is higher in females than in males [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Administration of Pegylated Arginase-1 Attenuates the Progression of Diabetic Retinopathy

Abdelrahman

Bunch

Sandow

et al. 2022

Cells

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Diabetic retinopathy (DR) is a serious complication of diabetes that results from sustained hyperglycemia, hyperlipidemia, and oxidative stress. Under these conditions, inducible nitric oxide synthase (iNOS) expression is upregulated in the macrophages (MΦ) and microglia, resulting in increased production of reactive oxygen species (ROS) and inflammatory cytokines, which contribute to disease progression. Arginase 1 (Arg1) is a ureohydrolase that competes with iNOS for their common substrate, L-arginine. We hypothesized that the administration of a stable form of Arg1 would deplete L-arginine’s availability for iNOS, thus decreasing inflammation and oxidative stress in the retina. Using an obese Type 2 diabetic (T2DM) db/db mouse, this study characterized DR in this model and determined if systemic treatment with pegylated Arg1 (PEG-Arg1) altered the progression of DR. PEG-Arg1 treatment of db/db mice thrice weekly for two weeks improved visual function compared with untreated db/db controls. Retinal expression of inflammatory factors (iNOS, IL-1β, TNF-α, IL-6) was significantly increased in the untreated db/db mice compared with the lean littermate controls. The increased retinal inflammatory and oxidative stress markers in db/db mice were suppressed with PEG-Arg1 treatment. Additionally, PEG-Arg1 treatment restored the blood–retinal barrier (BRB) function, as evidenced by the decreased tissue albumin extravasation and an improved endothelial ZO-1 tight junction integrity compared with untreated db/db mice.

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Correlation of Retinal Structure and Visual Function Assessments in Mouse Diabetes Models

Cited by 23 publications

References 36 publications

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

Peripheral retinal vessel whitening in patients with diabetes mellitus

Systemic Administration of Pegylated Arginase-1 Attenuates the Progression of Diabetic Retinopathy

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