Browsing by Subject "Retinal vessels"

Now showing 1 - 3 of 3
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    Per2-Mediated Vascular Dysfunction Is Caused by the Upregulation of the Connective Tissue Growth Factor (CTGF).
    (PLOS, 2016) Jadhav, Vaishnavi; Luo, Qianyi; M. Dominguez, James; Al-Sabah, Jude; Chaqour, Brahim; Grant, Maria B.; Bhatwadekar, Ashay D.; Department of Ophthalmology, IU School of Medicine
    Period 2-mutant mice (Per2m/m), which possess a circadian dysfunction, recapitulate the retinal vascular phenotype similar to diabetic retinopathy (DR). The vascular dysfunction in Per2m/m is associated with an increase in connective tissue growth factor (CTGF/CCN2). At the molecular level, CTGF gene expression is dependent on the canonical Wnt/β-catenin pathway. The nuclear binding of β-catenin to a transcription factor, lymphoid enhancer binding protein (Lef)/
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    Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice
    (American Diabetes Association, 2018-09) Beli, Eleni; Yan, Yuanqing; Moldovan, Leni; Vieira, Cristiano P.; Gao, Ruli; Duan, Yaqian; Prasad, Ram; Bhatwadekar, Ashay; White, Fletcher A.; Townsend, Steven D.; Chan, Luisa; Ryan, Caitlin N.; Morton, Daniel; Moldovan, Emil G.; Chu, Fang-I; Oudit, Gavin Y.; Derendorf, Hartmut; Adorini, Luciano; Wang, Xiaoxin X.; Evans-Molina, Carmella; Mirmira, Raghavendra G.; Boulton, Michael E.; Yoder, Mervin C.; Li, Qiuhong; Levi, Moshe; Busik, Julia V.; Grant, Maria B.; Pediatrics, School of Medicine
    Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR end points, including acellular capillaries and leukocyte infiltration. We hypothesized that IF-mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia. Compared with db/db mice on ad libitum feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number, villi length, and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR5, the TUDCA receptor, was found in the retinal primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a downstream target of TGR5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota toward species producing TUDCA and subsequent retinal protection by TGR5 activation.
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    Using optical coherence tomography angiography as a biomarker of retinopathy severity and treatment for diabetic retinopathy
    (Emory University, 2022-08-19) Scheive, Melanie; Reinhart, Kathryn L.; Hajrasouliha, Amir R.; Ophthalmology, School of Medicine
    Purpose: The goal was to evaluate optical coherence tomography angiography (OCT-A) as a biomarker to correlate retinal vessel density (VD) with diabetic retinopathy (DR) severity and visual acuity, as well as track antivascular endothelial growth factor (VEGF) treatment efficacy. Methods: This retrospective cohort study analyzed the automatically quantified VDs of the superficial vascular complex (SVC) and deep vascular complex (DVC), including the whole, foveal, and parafoveal VDs, on quality OCT-A scans in patients diagnosed with DR. A multivariate linear regression and analysis of variance (ANOVA) analysis compared VDs to DR severity, visual acuity, and demographic factors. A linear mixed analysis determined the effects of VD by whether anti-VEGF therapy was given to patients with OCT-A scans at multiple time points. Results: There was a positive correlation of the VDs in both the SVC whole and parafoveal VD and DVC parafoveal VD with decreased DR severity and increased visual acuity (p≤0.001). The DVC whole VD was also positively correlated with increased visual acuity (p<0.001). There was no difference in the VDs associated with anti-VEGF treatment over time. Conclusions: OCT-A VD shows promise for diagnosing and monitoring DR using DR severity and visual acuity. Anti-VEGF treatment had no significant effect (p=0.063) on vascular density in diabetic retinopathy.