Schuettauf Frank, Rejdak Robert, Walski Michal, Frontczak-Baniewicz Malgorzata, Voelker Michael, Blatsios Georgios, Shinoda Kei, Zagorski Zbigniew, Zrenner Eberhart, Grieb Pawel
Experimental Ophthalmology, University Eye Hospital, Roentgenweg 11, 72076, Tuebingen, Germany.
Acta Neuropathol. 2004 Apr;107(4):352-8. doi: 10.1007/s00401-003-0816-9. Epub 2004 Jan 24.
Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities, including glaucomatous loss of retinal ganglion cells (RGC). In the present study ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age (3, 6, 8 and 11 months) are described. By 3 months, RGC apoptosis characterized by electron-dense karioplasm and cytoplasm of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age, necrosis characterized by swelling and electron-rare cytoplasm appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. In these older animals myelin-like bodies, most probably representing the intracellular aggregates of phospholipids in irreversibly injured cells, were also seen. Photoreceptor cells were not affected at any age. Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood-borne inflammatory/phagocytosing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of RGC death. Retinal degeneration in 3- to 11-month-old DBA/2J mice partially resembles human pigment dispersion syndrome and pigmentary glaucoma with characteristic anterior segment changes and elevation of intraocular pressure. However, neovasculogenesis and myelin-like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.
DBA/2J品系小鼠会自发出现复杂的眼部异常，包括视网膜神经节细胞（RGC）的青光眼性丧失。在本研究中，描述了不同年龄（3、6、8和11个月）的DBA/2J小鼠视网膜神经变性的超微结构特征。到3个月时，观察到以神经节细胞电子致密核质和细胞质为特征的RGC凋亡。凋亡神经节细胞的发生率在6个月龄时达到峰值。超过这个年龄，以细胞质肿胀和电子密度降低为特征的坏死似乎成为细胞死亡的主要形式。穆勒胶质细胞活化随年龄增加，但没有白细胞浸润的迹象。在8个月和11个月时，在超微结构水平和临床检查中均发现了新生血管形成的迹象。在这些老龄动物中，还可见到髓样小体，最有可能代表不可逆损伤细胞中磷脂的细胞内聚集体。光感受器细胞在任何年龄均未受影响。我们的观察结果表明，DBA/2J小鼠的视网膜变性不涉及血源性炎症/吞噬细胞的募集，并且凋亡逐渐被坏死取代，成为RGC死亡的主要途径。3至11个月龄DBA/2J小鼠的视网膜变性部分类似于人类色素播散综合征和色素性青光眼，伴有特征性的眼前节改变和眼压升高。然而，在衰老过程中观察到新生血管形成和髓样小体。因此，DBA/2J模型作为青光眼模型需要谨慎解读。
