Schraermeyer Mareike, Schnichels Sven, Julien Sylvie, Heiduschka Peter, Bartz-Schmidt Karl-Ulrich, Schraermeyer Ulrich
Section of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, Tübingen, Germany.
Graefes Arch Clin Exp Ophthalmol. 2009 Nov;247(11):1493-504. doi: 10.1007/s00417-009-1146-y. Epub 2009 Jul 30.
To characterise ocular pigment abnormalities associated with iris atrophy in DBA/2J mice as a model for human pigment dispersion syndrome.
Immunohistochemistry, electron and light microscopy were performed to examine the eyes of DBA/2J mice ranging in age from 2.5 to 18 months old. The focus of our study was the description of the ultrastructural modifications in the irides of DBA/2J mice.
The DBA/2J mice presented modifications in the melanosomes in all the pigmented parts of the eye, including the retinal pigment epithelial cells and choroidal melanocytes of the ciliary pigment epithelium. The extracellular matrix of the iris stroma disappeared with ageing. Pigmented cells detached from the iris and migrated into the trabecular meshwork exclusively on the anterior iris surface. These cells were identified as macrophages by immunohistochemistry and electron microscopy. There was no evidence that melanocytes or iris pigment epithelial cells migrated into the trabecular meshwork, but they became more and more depigmented. The aqueous outflow was blocked by pigment-laden cells, but not by cellular debris or melanosomes. No substantial amount of extracellular melanosomes was observed.
The morphology of melanosomes is aberrant in all pigment cells in the eyes of DBA/2J mice. We conclude that the disease process begins with the transfer of both immature melanosomes from the iris pigment epithelium (IPE) and melanocytes to macrophages, which subsequently migrate into the trabecular meshwork. Accumulating macrophages cause a blockade of the chamber angle. As the disease progresses, the IPE, melanocytes and iris stroma, including blood vessels, disappear, leading to iris atrophy. It is speculated that the loss of these pigment cells is partly caused by reduction of the iris stroma.
将DBA/2J小鼠中与虹膜萎缩相关的眼部色素异常作为人类色素播散综合征的模型进行特征描述。
对年龄在2.5至18个月的DBA/2J小鼠的眼睛进行免疫组织化学、电子显微镜和光学显微镜检查。我们研究的重点是描述DBA/2J小鼠虹膜的超微结构改变。
DBA/2J小鼠眼睛所有色素沉着部位的黑素小体均出现改变，包括睫状色素上皮的视网膜色素上皮细胞和脉络膜黑素细胞。虹膜基质的细胞外基质随年龄增长而消失。色素细胞从虹膜脱离，仅在前房虹膜表面迁移至小梁网。通过免疫组织化学和电子显微镜鉴定这些细胞为巨噬细胞。没有证据表明黑素细胞或虹膜色素上皮细胞迁移至小梁网，但它们的色素沉着越来越少。房水流出被充满色素的细胞阻塞，但未被细胞碎片或黑素小体阻塞。未观察到大量细胞外黑素小体。
DBA/2J小鼠眼睛所有色素细胞中的黑素小体形态异常。我们得出结论，疾病过程始于未成熟黑素小体从虹膜色素上皮（IPE）和黑素细胞转移至巨噬细胞，随后巨噬细胞迁移至小梁网。积聚的巨噬细胞导致房角阻塞。随着疾病进展，IPE、黑素细胞和包括血管在内的虹膜基质消失，导致虹膜萎缩。据推测，这些色素细胞的丢失部分是由虹膜基质减少引起的。
