Systemic Reduction of Glut1 Normalizes Retinal Dysfunction, Inflammation, and Oxidative Stress in the Retina of Spontaneous Type 2 Diabetic Mice

Aiello, Jacob J.; Bogart, Maislin C.; Chan, Wai-Ting; Holoman, Nicholas C.; Trobenter, Timothy D.; Relf, Chloe E.; Kleinman, Dana M.; Vivo, Darryl C. De; Samuels, Ivy S.

doi:10.1016/j.ajpath.2023.04.003

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…Other retinal layers showing differences at specific ages included the RPE, photoreceptor outer segments (OS), and retina nerve fiber layer (RNFL) (Figure S1A). To determine if the mtDNA mutation burden had any effect on retinal cells' response to light flashes, electroretinography (ERG) was performed using a previously established protocol (Aiello et al, 2023). PolgD257A mice showed significantly decreased a-wave amplitude at 6 months of age (Figures 1E and 1G), indicating a functional reduction in rod photoreceptor cells at this time.…”

Section: Resultsmentioning

confidence: 99%

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Modeling aging and retinal degeneration with mitochondrial DNA mutation burden

Sturgis,

Singh,

Caron

et al. 2023

Preprint

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Somatic mitochondrial DNA (mtDNA) mutation accumulation has been observed in individuals with retinal degenerative disorders. To study the effects of aging and mtDNA mutation accumulation in the retina, a Polymerase gamma (POLG) deficiency model, the POLGD257Amutator mice (PolgD257A), was used. POLG is an enzyme responsible for regulating mtDNA replication and repair. Retinas of young and older mice with this mutation were analyzed in vivo and ex vivo to provide new insights into the contribution of age-related mitochondrial dysfunction due to mtDNA damage. Optical coherence tomography (OCT) image analysis revealed a decrease in retinal and photoreceptor thickness starting at 6 months of age in mice with the POLGD257Amutation compared to wild-type (WT) mice. Electroretinography (ERG) testing showed a significant decrease in all recorded responses at 6 months of age. Sections labeled with markers of different types of retinal cells, including cones, rods, and bipolar cells, exhibited decreased labeling starting at 6 months. However, electron microscopy analysis revealed differences in retinal pigment epithelium (RPE) mitochondria morphology beginning at 3 months. Interestingly, there was no increase in oxidative stress observed in the retina or RPE of POLGD257A mice. Additionally, POLGD257A RPE exhibited an accelerated rate of autofluorescence cytoplasmic granule formation and accumulation. Mitochondrial markers displayed decreased abundance in protein lysates obtained from retina and RPE samples. These findings suggest that the accumulation of mitochondrial DNA mutations leads to impaired mitochondrial function and accelerated aging, resulting in retinal degeneration.

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Section: Resultsmentioning

confidence: 99%

“…Retinal functions of mice were assayed after overnight dark adaptation as previously described (Aiello et al, 2023). Mice were anesthetized with 65 mg/kg sodium pentobarbital.…”

Section: Methodsmentioning

confidence: 99%

Modeling aging and retinal degeneration with mitochondrial DNA mutation burden

Sturgis,

Singh,

Caron

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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Are Hyperglycemia-Induced Changes in the Retina Associated with Diabetes-Correlated Changes in the Brain? A Review from Zebrafish and Rodent Type 2 Diabetes Models

Augustine-Wofford,

Connaughton,

McCarthy

2024

Biology

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Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.

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Systemic Reduction of Glut1 Normalizes Retinal Dysfunction, Inflammation, and Oxidative Stress in the Retina of Spontaneous Type 2 Diabetic Mice

Cited by 2 publications

References 37 publications

Modeling aging and retinal degeneration with mitochondrial DNA mutation burden

Modeling aging and retinal degeneration with mitochondrial DNA mutation burden

Are Hyperglycemia-Induced Changes in the Retina Associated with Diabetes-Correlated Changes in the Brain? A Review from Zebrafish and Rodent Type 2 Diabetes Models

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