Lavery Thomas C M, Rasmussen Carol A, Katz Alexander W, Kim Charlene B Y, Ver Hoeve James N, Miller Paul E, Sonnentag Peter J, Christian Brian J, Murphy Christopher J, Piwnica-Worms David R, Gammon Seth T, Qiu Xudong, Kaufman Paul L, Nork T Michael
Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Ocular Services On Demand (OSOD), LLC, Madison, WI, USA.
Curr Eye Res. 2025 Jan;50(1):93-100. doi: 10.1080/02713683.2024.2397028. Epub 2024 Sep 18.
Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.
Morphological studies were performed of the retinas of NHPs, specifically both rhesus () and cynomolgus macaques (), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy.
MMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2 weeks following the RNFL loss.
These data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.
微囊样黄斑变性（MMD）是一种在人类多种疾病中，视网膜内核层出现囊样空泡的病症。在此，我们报告非人类灵长类动物（NHPs）中出现的MMD，这些动物存在各种视网膜神经节细胞（RGC）病变，并评估MMD并非先于RGC丢失而是在其之后发生的假说。
对NHPs的视网膜进行形态学研究，具体包括恒河猴（）和食蟹猴（），在实验性青光眼（EG）、半侧视网膜透热脉络膜切开术（HEA）诱导后以及自发性特发性双侧视神经萎缩后发现了MMD。成像分析包括眼底照相、荧光素血管造影（FA）、光学相干断层扫描（OCT）、自适应光学扫描激光眼科显微镜检查（AOSLO）、光学显微镜和电子显微镜检查。
在患有EG的恒河猴和食蟹猴中均发现了类似人类OCT扫描所见的MMD。在13只接受过一次OCT成像的慢性EG食蟹猴中，13只动物中有6只被发现患有MMD。MMD在一只患有双侧视神经萎缩的食蟹猴中也很明显。在HEA之后，直到RNFL丢失至少2周后MMD才出现。
这些数据表明，MMD可能由与RGC丢失相关的逆行跨突触过程引起。MMD与炎症无关，在临床前监管研究中也不会是药物毒性的独立指标。由于其表现不一致且出现较晚，MMD作为临床生物标志物的用途有限。
