UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute, University College Dublin, Belfield, Dublin D4, Ireland.
Dis Model Mech. 2010 Mar-Apr;3(3-4):236-45. doi: 10.1242/dmm.003772. Epub 2010 Feb 8.
Approximately 2.5 million people worldwide are clinically blind because of diabetic retinopathy. In the non-proliferative stage, the pathophysiology of this ocular manifestation of diabetes presents as morphological and functional disruption of the retinal vasculature, and dysfunction of retinal neurons. However, it is uncertain whether the vascular and neuronal changes are interdependent or independent events. In addition, the identity of the retinal neurons that are most susceptible to the hyperglycaemia associated with diabetes is unclear. Here, we characterise a novel model of non-proliferative diabetic retinopathy in adult zebrafish, in which the zebrafish were subjected to oscillating hyperglycaemia for 30 days. Visual function is diminished in hyperglycaemic fish. Significantly, hyperglycaemia disrupts cone photoreceptor neurons the most, as evidenced by prominent morphological degeneration and dysfunctional cone-mediated electroretinograms. Disturbances in the morphological integrity of the blood-retinal barrier were also evident. However, we demonstrate that these early vascular changes are not sufficient to induce cone photoreceptor dysfunction, suggesting that the vascular and neuronal complications in diabetic retinopathy can arise independently. Current treatments for diabetic retinopathy target the vascular complications. Our data suggest that cone photoreceptor dysfunction is a clinical hallmark of diabetic retinopathy and that the debilitating blindness associated with diabetic retinopathy may be halted by neuroprotection of cones.
全世界约有 250 万人因糖尿病视网膜病变而临床失明。在非增殖期，这种糖尿病眼部表现的病理生理学表现为视网膜血管的形态和功能破坏，以及视网膜神经元的功能障碍。然而，血管和神经元的变化是否相互依存或独立尚不清楚。此外，与糖尿病相关的高血糖最易导致哪些视网膜神经元发生变化尚不清楚。在这里，我们在成年斑马鱼中建立了一种新型的非增殖性糖尿病视网膜病变模型，其中斑马鱼接受了 30 天的波动高血糖处理。高血糖鱼的视觉功能下降。值得注意的是，高血糖对锥状光感受器神经元的破坏最为严重，表现为明显的形态退化和功能失调的锥状介导的视网膜电图。血视网膜屏障的形态完整性也受到干扰。然而，我们证明这些早期的血管变化不足以引起锥状光感受器功能障碍，这表明糖尿病视网膜病变中的血管和神经元并发症可以独立发生。目前治疗糖尿病视网膜病变的方法针对血管并发症。我们的数据表明，锥状光感受器功能障碍是糖尿病视网膜病变的一个临床标志，并且与糖尿病视网膜病变相关的致残性失明可能通过对锥状光感受器的神经保护来阻止。
