Comparison of the neuroprotective effects of adrenoceptor drugs in retinal cell culture and intact retina.
Bibliographic record
Abstract
PURPOSE: The efficacy of beta1-adrenoceptor (AR)-selective (betaxolol and metoprolol) and nonselective (timolol) antagonists and the alpha2-AR agonist UK14,304 as retinal neuroprotectants was compared and contrasted in an in vitro glutamate excitotoxicity model. The ability of UK14,304, brimonidine, and betaxolol to alter glutamate-receptor-induced changes in intracellular calcium ([Ca2+]i) was also determined in isolated retinal neurons and retinal ganglion cells (RGCs) in an intact retina preparation. METHODS: Neuronal survival was measured in mixed retinal cell cultures treated for 24 hours with media containing 100 microM glutamate, with or without the addition of each of the drugs (1-1000 microM). Effects of glutamate on glia were also investigated in a C6 glioma cell line. Glutamate-induced changes in [Ca2+]i with and without UK14,304, and its analogue brimonidine were assessed by calcium-imaging techniques in retinal neurons in culture. The effect of betaxolol on [Ca2+]i was investigated in RGCs in intact rabbit retina. RESULTS: In cell cultures, 10-1000 microM glutamate resulted in a dose-dependent loss of neurons, but not of glia. The absence of glutamate toxicity in glia was confirmed in C6 glioma cells. Betaxolol, but not timolol or metoprolol, significantly increased survival (from 52% of control in glutamate-only to 78% with 10 microM betaxolol) after excitotoxic insult. UK14,304 also increased survival (from 62% of control in glutamate only to 109% and 101% of control with 10 and 100 microM UK14,304, respectively). This effect was blocked by the specific alpha2-antagonist, yohimbine. Both UK14,304 and brimonidine (10-100 microM) reduced glutamate-induced [Ca2+]i increases in retinal neurons in culture. The actions of the alpha2-agonists in reducing glutamate-induced [Ca2+]i increases were reduced by yohimbine (1 microM). Betaxolol (100 microM) reduced N-methyl-D-aspartate (NMDA)-induced increases of [Ca2+]i in RGCs in intact retina. CONCLUSIONS: Betaxolol reduced glutamate excitotoxicity in retinal neurons in vitro through a mechanism independent of beta-AR interactions. UK14,304, acting through alpha2-ARs, was also neuroprotective in vitro. The neuroprotective actions of betaxolol and the alpha2-agonists on retinal neurons may be due, at least in part, to a direct reduction of glutamate receptor-mediated increases of [Ca2+]i.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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".