更新于：2024-11-01

Snowflake Vitreoretinal Degeneration

雪花玻璃体视网膜变性

更新于：2024-11-01

基本信息

别名

SNOWFLAKE VITREORETINAL DEGENERATION、SVD、Snowflake degeneration in hereditary vitreoretinal degeneration

+ [5]

简介

Snowflake vitreoretinal degeneration (SVD) is characterised by the presence of small granular-like deposits resembling snowflakes in the retina, fibrillary vitreous degeneration and cataract. The prevalence is unknown but the disorder has been described in several families. Transmission is autosomal dominant and the causative gene has been localised to a small region on chromosome 2q36.

关联

项与雪花玻璃体视网膜变性相关的药物

RTC-14

靶点

Kir7.1

作用机制

KCNJ13基因调节剂

在研机构

University of Wisconsin Madison

原研机构

University of California, Los Angeles

在研适应症

莱伯先天性黑蒙 [+1]

非在研适应症

共济失调毛细血管扩张 [+1]

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与雪花玻璃体视网膜变性相关的临床结果

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100 项与雪花玻璃体视网膜变性相关的转化医学

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0 项与雪花玻璃体视网膜变性相关的专利（医药）

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项与雪花玻璃体视网膜变性相关的文献（医药）

2023-09-03·Ophthalmic Genetics

Phenotypic expansion of KCNJ13- associated snowflake vitreoretinal degeneration

Article

作者: Berrocal, Audina M. ; Sengillo, Jesse D. ; Iyer, Prashanth G. ; Negron, Catherin I. ; Yannuzzi, Nicolas A. ; Ashkenazy, Noy

INTRODUCTIONAn 18-year old highly myopic woman presented with bilateral retinoschisis associated with a unilateral macular hole in the right eye and vitreomacular traction in the left eye.METHODSGenetic studies disclosed a heterozygous pathogenic variant in the KCNJ13 gene was identified (c.484C>T (p.Arg162Trp)), consistent with a diagnosis of snowflake vitreoretinal degeneration (SVD).RESULTSWhile there were no corneal guttata, juvenile cataracts, or perivascular sheathing in this case, salient features of SVD included a fibrillar vitreous structure, crystalline retinopathy, and flattened optic nerves. The patient developed a FTMH in the left eye at 17 months follow up, followed by a rhegmatogenous retinal detachment (RRD) requiring 2 surgical repairs.CONCLUSIONThis case expands on the spectrum of clinical features in SVD, including retinoschisis and FTMH. It also characterizes optical coherence tomography findings in this rare disease entity. We emphasize the importance of using panel-based genetic testing to clinically distinguish and further define atypical vitreoretinopathies.

2023-03-01·American Journal of Physiology-Cell Physiology

The unique structural characteristics of the Kir 7.1 inward rectifier potassium channel: a novel player in energy homeostasis control

Review

作者: Hernandez, Ciria C. ; Dahir, Naima S. ; Peisley, Alys ; Gimenez, Luis E. ; Cone, Roger D.

The inward rectifier potassium channel Kir7.1, encoded by the KCNJ13 gene, is a tetramer composed of two-transmembrane domain-spanning monomers, closer in homology to Kir channels associated with potassium transport such as Kir1.1, 1.2, and 1.3. Compared with other channels, Kir7.1 exhibits small unitary conductance and low dependence on external potassium. Kir7.1 channels also show a phosphatidylinositol 4,5-bisphosphate (PIP2) dependence for opening. Accordingly, retinopathy-associated Kir7.1 mutations mapped at the binding site for PIP2 resulted in channel gating defects leading to channelopathies such as snowflake vitreoretinal degeneration and Leber congenital amaurosis in blind patients. Lately, this channel’s role in energy homeostasis was reported due to the direct interaction with the melanocortin type 4 receptor (MC4R) in the hypothalamus. As this channel seems to play a multipronged role in potassium homeostasis and neuronal excitability, we will discuss what is predicted from a structural viewpoint and its possible implications for hunger control.

2022-12-01·Progress in Neurobiology

Immune response in retinal degenerative diseases – Time to rethink?

Article

作者: Xu, Heping ; Chen, Mei

Retinal degeneration comprises a group of diseases whereby either the retinal neurons or the neurovascular unit degenerates leading to the loss of visual function. Although the initial cause varies in different conditions, inflammation is known to play an important role in disease pathogenesis. Recent advances in molecular and cell biology and systems biology have yielded unexpected findings, including the heterogeneity of immune cells in the degenerative retina, bidirectional neuron-microglia cross talk, and links to the gut microbiome. Here we discuss the immune response in retinal degenerative conditions, taking into account both regional (retinal) and systemic factors. We propose to classify retinal degeneration into dry and wet forms based on whether the blood-retinal barrier (BRB) is breached and fluid is accumulated in retinal parenchyma. The dry form has a relatively intact BRB and is characterised by progressive retinal thinning. Immune response to degenerative insults is dominated by the retinal defence system, which remains to be regulated by neurons. In contrast, the wet form has retinal oedema due to BRB damaged. Inflammation is executed by infiltrating immune cells as well as the retinal defence system. The gut microbiome will have easy access to the retina in wet retinal degeneration and may affect significantly retinal immune response.

项与雪花玻璃体视网膜变性相关的新闻（医药）

2022-01-03

·梅斯医学

JNNP:老年人淀粉样蛋白负荷的遗传性，一项基于澳大利亚老年双胞胎研究

几项大型研究检查了阿尔茨海默病 (AD) 的遗传情况。双胞胎研究提供了一个独特的机会来确定遗传和环境因素的相对重要性。表型如 AD，因为同卵 (MZ) 双胞胎共享 100% 的遗传物质，而异卵 (DZ) 双胞胎共享估计 50%。迄今为止，双胞胎研究估计散发性 AD 的遗传率在 48% 到 79% 之间，这表明迟发性 AD 的发展受到显着的遗传影响。然而，研究AD 遗传基础的一个主要限制是临床表型中出现的异质性。另一个挑战是 AD 是一种多组分疾病。除了 β-淀粉样斑块和过度磷酸化的 tau，潜在的病理生理机制还包括血管、免疫介导、胆固醇代谢和泛素化途径。因此，遗传和环境影响可能对这些成分中的每一个都有不同的影响。另一种方法是研究 AD 中间表型的遗传学，该表型可作为连续测量准确评估，例如 β-淀粉样蛋白。虽然单独的 β-淀粉样蛋白不足以引起 AD，但它是一种标志性的病理特征，在症状出现前的几十年里就积累了。大脑 β-淀粉样蛋白负荷的变异性在多大程度上是由遗传决定的，需要澄清，并且是最好的估计采用经典的双胞胎设计。此外，AD 和脑小血管病 (SVD) 病理通常在老年人中共同发生，并具有多种常见的血管危险因素，包括糖尿病、中年高血压、肥胖和吸烟。然而，在病理水平上，脑 SVD 是否促进淀粉样蛋白病理学仍然存在争议。8 在完全了解这些潜在的可改变风险因素之前，了解淀粉样蛋白负荷的比例是受遗传影响的，这一点很重要。本文主要研究：皮质 β-淀粉样蛋白负荷在全球和特定大脑区域的遗传性是什么？本文发表在《神经病学，神经外科学和精神病学杂志》上（Journal of Neurology, Neurosurgery & Psychiatry）. 参与者来自澳大利亚老年双胞胎研究 (OATS)。OATS 是一项基于社区的纵向研究，研究在澳大利亚双胞胎研究中心注册的 65 岁或以上双胞胎的衰老情况。纳入标准包括有能力同意、同意的双胞胎、完成了一些英语教育并且至少具有低平均智商。在可能的情况下，为每个人在 3 个月的时间范围内以及每对双胞胎之间收集临床和影像数据。该样本包括所有 OATS 参与者，这些参与者在 2012 年至 2017 年期间在两个地点（一个在悉尼，一个在墨尔本）接受了淀粉样蛋白 PET 扫描。为 OATS 参与者收集了详细的社会人口学、临床和神经心理学数据。一部分参与者可获得空腹血液病理学数据，包括空腹血糖（n=162）和空腹血脂（高密度脂蛋白、低密度脂蛋白、甘油三酯和总胆固醇；n=163)。使用标准方法从外周血样本中提取 DNA。 Taqman 分析（Applied Biosystems Inc，Foster City，California，USA）的两个单核苷酸多态性（rs7412、rs429358）被用于确定 APOE ε2/3/4 基因型。从位于悉尼和墨尔本的两个中心获得 206 名淀粉样蛋白 PET 参与者中的 176 名的 MRI 数据。在悉尼，使用了 Phillips 3T Achievar Quasar Dual 扫描仪（n=85）。在墨尔本，使用了 3T Siemens MAGMETOM Trio 扫描仪 (n=91)。对原始扩散张量成像数据进行目视检查以排除任何严重的伪影，这导致四次扫描被从处理中移除（留下 206 名参与者中的 172 名）。该研究共包括 206 名参与者，其中包括 61 对 MZ 双胞胎，平均年龄：71.98（SD 6.43）岁）和 42 对 DZ 双胞胎，平均年龄：71.14（ 5.15) 年）。大多数人没有认知障碍。使用 SUVR方法发现， β-淀粉样蛋白负荷的遗传力中等（h2：0.412，95% CI：0.154 至 0.616）。在皮质区域，β-淀粉样蛋白的遗传力从前扣带回皮层的 0.203（95% CI：0.000 至 0.427）到上顶叶的 0.540（95% CI：0.343 至 0.686）不等。APOE ɛ4 携带者状态与淀粉样蛋白负荷显着相关，通过 SUVR 测量的 β-淀粉样蛋白与 WMHV 或 PSMD 之间没有显着的遗传或环境相关性。目前的研究结果表明 β-淀粉样蛋白的积累在大多数受中等遗传影响，易受重大环境因素的影响。遗传力的区域差异难以解释。眶额皮质和顶叶上叶是我们研究中遗传性最大的两个区域，通常与早期和更大程度的 β-淀粉样蛋白积累相关。重要的特定环境影响——即部分可改变的因素——有助于 β-淀粉样蛋白的积累。血管危险因素在淀粉样蛋白、tau 蛋白和神经变性（“血管假说”）发展中的作用在过去十年中获得了一些关注，突出了大脑微循环功能障碍在 AD 中导致非淀粉样蛋白依赖性神经元损伤的核心作用。总之，淀粉样蛋白沉积是阿尔茨海默病的早期标志，受到中等遗传影响，这表明可能需要干预环境影响因素。