This open-access review of research on visual pathologies in diabetes is interesting, if depressing. Abstract below, but the even shorter version is that microvascular hemorrhages like the ones picked up on your annual eye exam are a lagging indicator of other forms of retinal dysfunction. There are significant neural changes in the retina that are detectable both behaviorally and functionally even before vascular degeneration takes place. Some sketches of the mechanisms underlying those changes and possible clinical interventions on them, but the latter are mostly speculative at this point.
Abstract: Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina. They also exhibit reduced contrast sensitivity. These early changes, especially those due to dysfunction in the inner retina, are also seen in rodent models of diabetes in the early stages of the disease. Rodent models of diabetes exhibit several neuronal mechanisms, such as reduced evoked GABA release, increased excitatory glutamate signaling, and reduced dopamine signaling, that suggest specific neuronal deficits. This suggests that understanding neuronal deficits may lead to early diabetes treatments to ameliorate neuronal dysfunction.
Article: https://www.annualreviews.org/content/journals/10.1146/annurev-vision-111022-123810
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Thanks for that. It’s really interesting. It also supports the theory that rapidly lowering A1c doesn’t cause retinopathy so much as exacerbate an existing but unnoticed condition.
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I’m not sure this review sheds light on that, unfortunately. Two things are specifically correlated with heightened A1C: (1) decreased contrast sensitivity and (2) changes to the photopic negative response, a component of retinal electrogram measurements. That doesn’t inform about what happens if A1C changes, though. In fact, the author notes that these conclusions are hard to draw: “There can also be significant variations in blood glucose levels among studies using rodent diabetic models, which would be interesting to correlate with changes in ERG waves. However, a systematic review concluded that most papers do not provide raw data for ERG measurements, so the magnitude of effects is difficult to determine (Lelyte et al. 2022).”
For that matter, it’s even possible that the neural dysfunction is not strongly correlated with A1C. Not all pathologies of diabetes are mediated by hyper/hypoglycemia. What’s definitely true is that most of the clinical tests for retinal dysfunction are missing these early degenerative changes.
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Thanks for sharing this review! It’s fascinating (if a bit unsettling) to see how retinal dysfunction in diabetes precedes vascular damage. The idea of treating diabetic retinopathy as a neurovascular disease makes sense, and it’s intriguing to consider potential early interventions—though, as noted, they seem largely speculative for now. Definitely highlights the importance of early screening beyond just microvascular signs.
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