Sdobnikova Svetlana V, Makhotin Sergey S, Revishchin Alexander V, Sysoeva Veronika Y, Pavlova Galina V, Sdobnikova Lyubov E
Department of Aging-associated Diseases, Medical Scientific and Educational Institute of Lomonosov Moscow State University, Moscow, Russia.
Department of Ophthalmology, Medical Scientific and Educational Institute of Lomonosov Moscow State University, Moscow, Russia.
Front Cell Neurosci. 2025 Apr 23;19:1571596. doi: 10.3389/fncel.2025.1571596. eCollection 2025.
To investigate the topographic relationship between glial tissue and active neovessels in epiretinal membranes (ERMs) in proliferative diabetic retinopathy (PDR).
Phase-contrast and immunofluorescence microscopy were performed on 17 surgically removed ERMs from 17 eyes of 17 PDR patients. Clusters of active neovessels and the surrounding posterior hyaloid membrane were excised en bloc. ERMs were immunolabeled with anti-glial fibrillary acidic protein (GFAP) antibodies to identify glia, and with anti-collagen IV or anti-von Willebrand factor (VWF) antibodies to identify neovessels. All ERMs were analyzed as whole-mounted preparations, each including the area of leading neovessels.
GFAP-immunopositive glial cells (GCs) were identified in 11 of 17 specimens (65%). These cells also co-expressed type IV collagen. Fibrils immunopositive for type IV collagen (GFAP-negative) were detected in all cases. The topography, structure, and GFAP immunoreactivity distinguished GCs from GFAP-negative hyalocytes. GCs had bipolar shape, small cell bodies, very long, sparsely branching, bidirectional processes, and showed a tendency to form clumps. The structure of GCs was more consistent with that of Müller cells. In all ERMs, the majority of GCs were localized around the epicenter of neovascular clusters (where neovessels branched from the maternal vessel), which also corresponded to the highest density of collagen fibrils. In four cases (23.5%), GCs were also identified in the area of the leading capillaries; however, no signs of direct interaction between GCs and developing neovessels was observed in these cases.
Our study found no evidence of direct interaction between GCs and leading neovessels in PDR, opposite to what was shown in embryonic retinal angiogenesis. The findings may suggest that the presence of GCs near the neovascular cluster epicenter and around leading capillaries reflects different phases of the proliferative process in PDR. In the first case, GFAP+ cells appear to be involved in the involution of neovessels, which occurs during vascular remodeling or regression. In the second case, when GCs were located around the leading neovessels, their proliferation was not directly related to blood vessel formation; in our opinion, these processes may represent independent events that might have common triggers.
研究增殖性糖尿病视网膜病变（PDR）患者视网膜前膜（ERM）中神经胶质组织与活跃新生血管之间的地形关系。
对17例PDR患者的17只眼睛手术切除的ERM进行相差显微镜和免疫荧光显微镜检查。将活跃新生血管簇及其周围的后玻璃体膜整块切除。用抗胶质纤维酸性蛋白（GFAP）抗体对ERM进行免疫标记以识别神经胶质细胞，用抗IV型胶原或抗血管性血友病因子（VWF）抗体识别新生血管。所有ERM均作为整装标本进行分析，每个标本都包括主要新生血管区域。
在17个标本中的11个（65%）中鉴定出GFAP免疫阳性的神经胶质细胞（GC）。这些细胞还共表达IV型胶原。在所有病例中均检测到IV型胶原免疫阳性（GFAP阴性）的纤维。GC的地形、结构和GFAP免疫反应性使其与GFAP阴性的玻璃体细胞区分开来。GC呈双极形状，细胞体小，有非常长、稀疏分支的双向突起，并显示出形成团块的趋势。GC的结构与Müller细胞的结构更一致。在所有ERM中，大多数GC位于新生血管簇的中心（新生血管从母血管分支处）周围，此处也是胶原纤维密度最高的地方。在4例（23.5%）中，在主要毛细血管区域也鉴定出了GC；然而，在这些病例中未观察到GC与发育中的新生血管之间有直接相互作用的迹象。
我们的研究未发现PDR中GC与主要新生血管之间存在直接相互作用的证据，这与胚胎视网膜血管生成中的情况相反。这些发现可能表明，新生血管簇中心和主要毛细血管周围GC的存在反映了PDR增殖过程的不同阶段。在第一种情况下，GFAP+细胞似乎参与了新生血管的退化，这发生在血管重塑或消退期间。在第二种情况下，当GC位于主要新生血管周围时，它们的增殖与血管形成没有直接关系；我们认为，这些过程可能代表了可能有共同触发因素的独立事件。
