Keilhoff Gerburg, Titze Maximilian, Ebmeyer Uwe
Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, Magdeburg, Germany.
Department of Anesthesiology, Medical Faculty, University of Magdeburg, Magdeburg, Germany.
Restor Neurol Neurosci. 2021;39(4):267-289. doi: 10.3233/RNN-211174.
Stroke-related loss of vision is one of the residual impairments, restricting the quality of life. However, studies of the ocular manifestations of asphyxia cardiac arrest/resuscitation (ACA/R) have reported very heterogeneous results.
We aimed to evaluate the ACA/R-induced degeneration pattern of the different retinal cell populations in rats using different immuno-histological stainings.
The staining pattern of toluidine blue and the ganglion cell markers β-III-tubulin and NeuN; the calcium-binding protein parvalbumin, indicating ganglion, amacrine, and horizontal cells; calretinin D28k, indicating ganglion and amacrine cells; calbindin, indicating horizontal cells; Chx 10, indicating cone bipolar cells; PKCα, indicating ON-type rod bipolar cells; arrestin, indicating cones; and rhodopsin, a marker of rods, as well as the glial cell markers GFAP (indicating astroglia and Müller cells) and IBA1 (indicating microglia), were evaluated after survival times of 7 and 21 days in an ACA/R rat model. Moreover, quantitative morphological analysis of the optic nerve was performed. The ACA/R specimens were compared with those from sham-operated and completely naïve rats.
ACA/R-induced effects were: (i) a significant reduction of retinal thickness after long-term survival; (ii) ganglion cell degeneration, including their fiber network in the inner plexiform layer; (iii) degeneration of amacrine and cone bipolar cells; (iv) degeneration of cone photoreceptors; (v) enhanced resistance to ACA/R by rod photoreceptors, ON-type rod bipolar and horizontal cells, possibly caused by the strong upregulation of the calcium-binding proteins calretinin, parvalbumin, and calbindin, counteracting the detrimental calcium overload; (vi) significant activation of Müller cells as further element of retinal anti-stress self-defense mechanisms; and (vii) morphological alterations of the optic nerve in form of deformed fibers.
Regardless of the many defects, the surviving neuronal structures seemed to be able to maintain retinal functionality, which can be additionally improved by regenerative processes true to the "use it or lose it" dogma.
与中风相关的视力丧失是残留损伤之一，限制了生活质量。然而，关于窒息性心脏骤停/复苏（ACA/R）眼部表现的研究报告结果差异很大。
我们旨在使用不同的免疫组织化学染色评估ACA/R诱导的大鼠不同视网膜细胞群的退化模式。
在ACA/R大鼠模型中，分别在存活7天和21天后评估甲苯胺蓝以及神经节细胞标志物β-III-微管蛋白和NeuN的染色模式；钙结合蛋白小白蛋白，表明神经节、无长突和水平细胞；钙视网膜蛋白D28k，表明神经节和无长突细胞；钙结合蛋白，表明水平细胞；Chx 10，表明视锥双极细胞；PKCα，表明ON型视杆双极细胞；抑制蛋白，表明视锥细胞；视紫红质，视杆细胞的标志物，以及胶质细胞标志物GFAP（表明星形胶质细胞和穆勒细胞）和IBA1（表明小胶质细胞）。此外，对视神经进行了定量形态分析。将ACA/R标本与假手术和未处理的大鼠标本进行比较。
ACA/R诱导的影响包括：（i）长期存活后视网膜厚度显著降低；（ii）神经节细胞退化，包括其在内网状层的纤维网络；（iii）无长突和视锥双极细胞退化；（iv）视锥光感受器退化；（v）视杆光感受器、ON型视杆双极细胞和水平细胞对ACA/R的抵抗力增强，这可能是由于钙结合蛋白钙视网膜蛋白、小白蛋白和钙结合蛋白的强烈上调，抵消了有害的钙超载；（vi）穆勒细胞显著激活，作为视网膜抗应激自我防御机制的进一步要素；（vii）视神经形态改变，表现为纤维变形。
尽管存在许多缺陷，但存活的神经元结构似乎能够维持视网膜功能，根据“用进废退”原则，再生过程可进一步改善视网膜功能。
