Drusen and Pro-inflammatory Mediators in the Post-Mortem Human Eye
Bibliographic record
Abstract
With age and drusen accumulation, the environment of the eye tends to shift more towards a pro-inflammatory state (Figure 6) through either IL-1β and/or possibly IFN pathways. Little change is induced in the complement inhibitor, CFI, in association with drusen, suggesting a failure to activate protective mechanisms against complement activation. Alternatively, the lack of change in CFI accumulation level could indicate that that the pro-inflammatory actions of drusen may not yet be enough to trigger inhibition of the complement cascade in healthy eye tissue. Here, we identified three inflammatory molecules in the postmortem human eye, p-STAT3, CXCL-10, and CXCL-11, to be strongly correlated with the presence of drusen within a population controlled for age (≤57 years old, Figure 6). This pattern of accumulation suggests that these molecules are closely involved with the presence of drusen rather than with aging, and may represent a predisposition toward AMD pathogenesis. A recent microarray study on mouse RPE cells reported expression changes in over 315 genes associated with advanced age [48]. Many pathways they identified were also found in our prior microarray study (unpublished observation) [16]. Similarly, Chen et al. [49] found that the mouse neuroretina displayed age-related upregulation of the complement cascade and activation of retinal microglia [49]. Curiously, neither study found expression changes in any of the gene products examined in this study. It is important to note that drusen-like deposits have not been documented in wild-type-mouse eyes [50]. Thus, one interpretation for this discrepancy may be that the genes identified in our microarray studies, and specifically the gene products studied here reflect a drusen-specific response rather than a general response to aging. Our studies now set the stage for future experiments testing the function of each of these potential mediators in the pathogenesis of AMD. One approach might involve assessing the response of each mediator following Aβ and/or AGE injection into young wild-type mice to determine degree of mimicry to AMD pathology. Figure 6 Summary diagram depicting the distribution of IL-1β, RSAD2, p-STAT3, and CXCL-10/11 immunoreactivity in post-mortem eye tissue with respect to aging and present of drusen. Icons denote the relative immunostaining of each molecule in a given retinallocation. ... Acknowledgments We thank Jonathan Tang, Jonathan Coleman, and Dr. Ian Clark for discussion and editing of the manuscript. This work was funded by Canadian Institutes of Health Research (CIHR-MOP-97806) to J.A.M. Grant Support Supported by Canadian Institutes of Health Research (CIHR) Grant# MOP-97806 (to JAM).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".