Zucker Charles L, Bernstein Paul S, Schalek Richard L, Lichtman Jeff W, Dowling John E
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, United States.
Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, United States.
Front Ophthalmol (Lausanne). 2024 Jul 30;4:1428777. doi: 10.3389/fopht.2024.1428777. eCollection 2024.
Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional Müller glial cell loss in the retina and the amino acid serine synthesized by Müller cells, the disease is functionally confined to a central retinal region - the MacTel zone.
We have used high-throughput multi-resolution electron microscopy techniques, optimized for disease analysis, to study the retinas from two women, mother and daughter, aged 79 and 48 years respectively, suffering from MacTel.
In both eyes, the principal observations made were changes specific to mitochondrial structure both outside and within the MacTel zone in all retinal cell types, with the exception of those in the retinal pigment epithelium (RPE). The lesion areas, which are a hallmark of MacTel, extend from Bruch's membrane and the choriocapillaris, through all depths of the retina, and include cells from the RPE, retinal vascular elements, and extensive hypertrophic basement membrane material. Where the Müller glial cells are lost, we have identified a significant population of microglial cells, exclusively within the Henle fiber layer, which appear to ensheathe the Henle fibers, similar to that seen normally by Müller cells.
Since Müller cells synthesize retinal serine, whereas retinal neurons do not, we propose that serine deficiency, required for normal mitochondrial function, may relate to mitochondrial changes that underlie the development of MacTel. With mitochondrial changes occurring retina-wide, the question remains as to why the Müller cells are uniquely susceptible within the MacTel zone.
2型黄斑毛细血管扩张症（MacTel）是一种罕见的迟发性、缓慢进展性黄斑变性。该疾病与视网膜局部Müller神经胶质细胞丢失以及由Müller细胞合成的氨基酸丝氨酸有关，其功能局限于视网膜中央区域——MacTel区。
我们使用了针对疾病分析进行优化的高通量多分辨率电子显微镜技术，来研究两名分别为79岁和48岁的患MacTel的女性（母亲和女儿）的视网膜。
在双眼观察到的主要情况是，除视网膜色素上皮（RPE）细胞外，所有视网膜细胞类型在MacTel区内和区外的线粒体结构均有特定变化。作为MacTel标志的病变区域从 Bruch膜和脉络膜毛细血管层延伸至视网膜各层深度，包括RPE细胞、视网膜血管成分以及广泛增生的基底膜物质。在Müller神经胶质细胞缺失的区域，我们在Henle纤维层内发现了大量小胶质细胞，这些小胶质细胞似乎包裹着Henle纤维，类似于正常情况下Müller细胞的包裹方式。
由于Müller细胞合成视网膜丝氨酸，而视网膜神经元不合成，我们推测正常线粒体功能所需的丝氨酸缺乏可能与MacTel发生发展的线粒体变化有关。鉴于线粒体变化在整个视网膜中发生，问题仍然是为什么Müller细胞在MacTel区内特别易受影响。
