Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and Protracted Microvascular Retinopathy
Bibliographic record
Abstract
Purpose: To characterize retinal mitochondrial respiration associated with type 2 diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus Arvicanthis, species niloticus). Methods: Nile rats were fed a standard rodent diet that resulted in rising glucose levels from 6 months. Age-matched control animals were fed a high-fiber diet that prevented diabetes up to 18 months. The functional status of specific retinal mitochondrial components and mitochondrial outer membrane integrity were studied by using high-resolution respirometry. Ocular complications were documented with funduscopy, electroretinography (ERG), and trypsin digestion of retinal vasculature. Results: Mitochondrial functional changes were detected during hyperinsulinemia with maintained normoglycemia (2 months), corresponding to stage 1 of human T2D. Our data showed increased contribution of mitochondrial respiration through the NADH pathway relative to maximal oxidative phosphorylation capacity, with simultaneous electron entry into NADH (Complex I and related dehydrogenases) and succinate (Complex II) pathways. These compensatory events coincided with compromised mitochondrial outer membrane integrity. The first clinical sign of retinopathy (pericyte loss) was only detected at 12 months (after 6 months of sustained hyperglycemia) alongside a common ocular complication of diabetes, cataractogenesis. Further prolongation of hyperglycemia (from 12 to 18 months) led to capillary degeneration and delayed photopic ERG oscillatory potentials. Conclusions: Oxidative phosphorylation compensatory changes in the retina can be detected as early as 2 months, before development of hyperglycemia, and are associated with reduced mitochondrial outer membrane integrity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".