Complications of Diabetes Unit, Diabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Centro per la Riferibilità Metrologica in Medicina di Laboratorio (CIRME), Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, 20133 Milan, Italy.
Int J Mol Sci. 2023 Aug 11;24(16):12672. doi: 10.3390/ijms241612672.
Diabetes-driven retinal neurodegeneration has recently been shown to be involved in the initial phases of diabetic retinopathy, raising the possibility of setting up a preventive strategy based on early retinal neuroprotection. To make this possible, it is crucial to identify a biomarker for early retinal neurodegeneration. To this end, in this study, we verified and confirmed that, in the Akita mouse model of diabetes, the thinning of the retinal nerve fiber layer/ganglion cell layer (the RNFL/GCL-the layer that contains the retinal ganglion cells) precedes the death of these same cells, suggesting that this dysfunction is a possible biomarker of retinal neurodegeneration. We then confirmed the validity of this assumption by starting a neuroprotective treatment (based on nerve growth factor eye drops) in concert with the first demonstration of RNFL/GCL thinning. In this way, it was possible not only to avoid the loss of retinal ganglion cells but also to prevent the subsequent development of the microvascular stage of diabetic retinopathy. In conclusion, in the case of diabetes, the thinning of the RNFL/GCL appears to be both a valid biomarker and a pharmacological target of diabetic retinopathy; it precedes the development of vascular dysfunctions and represents the ideal starting point for prevention.
糖尿病驱动的视网膜神经退行性变最近被证明与糖尿病性视网膜病变的初始阶段有关,这为基于早期视网膜神经保护的预防策略提供了可能性。为此,确定早期视网膜神经退行性变的生物标志物至关重要。为此,在这项研究中,我们验证并证实,在糖尿病的 Akita 小鼠模型中,视网膜神经纤维层/节细胞层(包含视网膜节细胞的层)变薄先于这些细胞死亡,表明这种功能障碍是视网膜神经退行性变的一个可能的生物标志物。然后,我们通过在首次显示视网膜神经纤维层/节细胞层变薄时开始神经保护治疗(基于神经生长因子眼药水),证实了这一假设的有效性。通过这种方式,不仅可以避免视网膜节细胞的丧失,还可以预防糖尿病性视网膜病变的微血管阶段的后续发展。总之,在糖尿病的情况下,视网膜神经纤维层/节细胞层变薄似乎既是一种有效的生物标志物,也是糖尿病性视网膜病变的药物靶点;它先于血管功能障碍的发展,是预防的理想起点。