更新于：2024-05-01

Retinal Dysplasia

视网膜发育不良

更新于：2024-05-01

基本信息

别名

Dysplasia, Retinal、Dysplasias, Retinal、Retinal Dysplasia

+ [13]

简介

Congenital, often bilateral, retinal abnormality characterized by the arrangement of outer nuclear retinal cells in a palisading or radiating pattern surrounding a central ocular space. This disorder is sometimes hereditary.

关联

项与视网膜发育不良相关的药物

Voretigene Neparvovec

靶点

RPE65

作用机制

RPE65基因转移

在研机构

Spark Therapeutics, Inc. [+4]

原研机构

The Children's Hospital of Philadelphia

在研适应症

遗传性视网膜营养不良 [+4]

非在研适应症

视网膜色素变性

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2017-12-19

Retinalamin

靶点-

作用机制-

在研机构

Geropharm LLC

原研机构

Geropharm LLC

在研适应症

糖尿病性视网膜病变 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

俄罗斯

首次获批日期2008-01-01

Timrepigene emparvovec

靶点

REP1

作用机制

REP1刺激剂 [+1]

在研机构

NightstaRx Ltd. [+2]

原研机构

University of Oxford

在研适应症

无脉络膜症 [+2]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

项与视网膜发育不良相关的临床试验

CTRI/2024/02/063005 / Not yet recruitingN/AIIT

Safety and efficacy of oral Gabapentin in perioperative care of patients undergoing vitrectomy procedures-A randomized control trial. - NIL

开始日期2024-03-03

申办/合作机构-

ACTRN12623001174673 / RecruitingN/A

Assessing cardiovascular risk by integrating retinal photography and artificial intelligence at primary care settings

开始日期2023-06-19

申办/合作机构-

CTRI/2022/12/047921 / Not yet recruitingN/A

Changes in ocular biomechanics following vitreoretinal surgery and its effect on intraocular pressure measurement using different modalities.

开始日期2022-12-10

申办/合作机构-

100 项与视网膜发育不良相关的临床结果

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100 项与视网膜发育不良相关的转化医学

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0 项与视网膜发育不良相关的专利（医药）

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442

项与视网膜发育不良相关的文献（医药）

2024-02-15·Experimental cell research

Loss-of-function of kinesin-5 KIF11 causes microcephaly, chorioretinopathy, and developmental disorders through chromosome instability and cell cycle arrest.

Article

作者: Yi Zhou ; Meng-Fei Xu ; Jie Chen ; Jing-Lian Zhang ; Xin-Yao Wang ; Min-Hui Huang ; Ya-Lan Wei ; Zhen-Yu She

Kinesin motors play a fundamental role in development by controlling intracellular transport, spindle assembly, and microtubule organization. In humans, patients carrying mutations in KIF11 suffer from an autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR). While mitotic functions of KIF11 proteins have been well documented in centrosome separation and spindle assembly, cellular mechanisms underlying KIF11 dysfunction and MCLMR remain unclear. In this study, we generate KIF11-inhibition chick and zebrafish models and find that KIF11 inhibition results in microcephaly, chorioretinopathy, and severe developmental defects in vivo. Notably, loss-of-function of KIF11 causes the formation of monopolar spindle and chromosome misalignment, which finally contribute to cell cycle arrest, chromosome instability, and cell death. Our results demonstrate that KIF11 is crucial for spindle assembly, chromosome alignment, and cell cycle progression of progenitor stem cells, indicating a potential link between polyploidy and MCLMR. Our data have revealed that KIF11 inhibition cause microcephaly, chorioretinopathy, and development disorders through the formation of monopolar spindle, polyploid, and cell cycle arrest.

2023-09-25·Fetal and pediatric pathology

Prenatal Array-CGH Detection of 3q26.32q26.33 Interstitial Deletion Encompassing the SOX2 Gene: Ultrasound, Pathological, and Cytogenetic Findings.

Article

作者: Maria Paola Bonasoni ; Giuseppina Comitini ; Mariangela Pati ; Veronica Bizzarri ; Veronica Barbieri ; Maria Marinelli ; Stefano Giuseppe Caraffi ; Roberta Zuntini ; Marzia Pollazzon ; Andrea Palicelli ; Livia Garavelli

Background: SOX2 disorders are associated with anophthalmia-esophageal-genital syndrome or microphthalmia, syndromic 3 (MCOPS3- # 206900). Case Report: We describe a third fetal case with a de novo 3q26.32q26.33 deletion extending for 4.31 Mb, detected in a 15-week fetus. After legal interruption of pregnancy, at autopsy, the fetus presented bilateral microphthalmia, right cleft lip and palate, bilateral cerebral ventriculomegaly and dilated third ventricle, microcystic left lung, and intestinal malrotation. Histologically, the left lung showed congenital pulmonary airway malformation (CPAM) type 2. Retinal dysplasia was found in both eyes. Discussion/Conclusion: The human SOX2 gene (OMIM #184429) is located on chromosome 3 at position q26.3-27 and encodes a transcription factor involved in the development of the central and peripheral nervous systems, retina, and lung. In our case, the combination of cerebral, retinal, and pulmonary anomalies, not previously described, are consistent with SOX2 haploinsufficiency due to chromosomal deletion.

2023-08-30·European journal of ophthalmology

The contribution of indocyanine green angiography in a case of unilateral retinal pigment epithelium dysgenesis.

Article

作者: Enrique Cervera-Taulet ; Javier Montero-Hernández ; Clara Monferrer Adsuara ; Jose S Pulido

PURPOSE:

To further enhance understanding of the expanded clinical spectrum of unilateral retinal pigment epithelium dysgenesis (URPED) via numerous imaging modalities including novel markers of highly detailed indocyanine green angiography (ICGA) features.

METHODS:

Retrospective, observational, case report.

RESULTS:

URPED in this patient is expressed as a solitary, flat and pigmented lesion in the posterior pole with RPE hyperplasia and atrophic changes. An epiretinal membrane (ERM) causing fine, tortuous retinal vessels and retinal folds was observed. Green and blue excitation light fundus autofluorescence showed a biphasic appearance with hypoautofluorescent rounded lesions and a reticular configuration of normal RPE. Fundus fluorescein angiography revealed diffuse hypofluorescence and hyperfluorescent wisps of leakage in late-phases. Early-phase of ICGA evidenced diffuse hypocianescence and a delineated hypercianescent scalloped margin appeared in the late-phase, together with focal hypocianescent spots. SD-OCT demonstrated irregularity of the RPE with fibrosis and hyperplastic changes combined with atrophic areas. Flat RPE detachments intermingled with healthy-appearing RPE were also observed together with thinning of the outer retina. ERM with thickening and disorganization involving the whole retina was present. Optical coherence tomography angiography (14 × 14 mm) revealed an oval shape foveal avascular zone and vascular anomalies such as tortuosity and looping.

CONCLUSION:

URPED is an extremely rare clinical entity with only a few cases reported. In this case the almost pathognomonic differential features of URPED were best appreciated with ICGA imaging. To our knowledge, this is the first reported case of URPED with these abnormal findings on ICGA meaning it could be part of the spectrum of the disease.

项与视网膜发育不良相关的新闻（医药）

2024-02-27

·奇点网

《细胞》：颠覆认知！中国科学家首次发现，肠菌竟然能直接参与遗传性视网膜变性，抗生素治疗或可阻止疾病进展丨科学大发现

*仅供医学专业人士阅读参考遗传性视网膜变性是工业化国家工作年龄人群失明的最常见原因。遗传性视网膜变性是一组异质性疾病的总称，它实际上有250多个相关基因，其中之一就是CRB1。CRB1基因突变常见于Leber先天性黑朦（LCA）和视网膜色素变性（RP），这两种疾病分别有10-15%和4%可归因于CRB1突变。但是令人惊讶的是，在CRB1突变导致的视网膜变性中，还有肠菌的参与。今日，《细胞》杂志发表了来自广州医科大学魏来、中山大学张峰/魏泓、英国伦敦大学学院Richard Lee团队发表的新论文，研究者们发现，CRB1同时参与视网膜和结肠上皮屏障功能，CRB1突变破坏了这两道屏障，为肠菌的眼部转移大开方便之门。使用抗生素进行全身治疗能够有效缓解肠菌导致的视网膜损伤，阻止视网膜进一步变性；针对肠道进行局部基因治疗，也能阻止疾病进展。虽然这不能让已经损伤的视网膜原地复活，但抗生素简单有效，也算得上是种不错的治疗选择。论文题图研究使用的Rd8小鼠在Crb1基因处存在移码突变，会提前引入终止子，导致CRB1蛋白的降解。Rd8小鼠与Crb1敲除小鼠具有相似的视网膜变性表型，经常用于相关研究。眼底镜检查中可见Rd8小鼠出现了眼底白斑，这是进行性视网膜发育不良和变性的典型特征。有意思的是，研究者发现，在胚胎阶段并非所有Rd8小鼠都存在视网膜发育不良，但在出生后12天小鼠都出现了典型病变。研究者认为，这代表着一种可能性——Crb1缺失之外，环境因素也参与了Rd8小鼠视网膜变性的发生。使用RNA测序，研究者发现，Rd8小鼠视网膜的差异表达基因中，参与“细菌与病毒识别”有显著的高表达。此外，参与促炎的基因以及小胶质细胞和巨噬细胞浸润的基因也很丰富。研究者由此产生了一个大胆的猜测，Rd8小鼠视网膜变性存在病原体的参与，而且伴有局部的先天免疫反应。Rd8视网膜变性有环境的参与之所以说这个猜测大胆，是因为在传统观点中，眼部和大脑一样，防御严密非常，一般不会有病原体存在。但是在一番检查之后，研究者还真在Rd8小鼠视网膜处发现了7种细菌的少量存在。这些细菌仅存在于病变的白斑内部，非病变区是没有的。在Rd8视网膜处发现了7种细菌这些细菌是打哪儿来的呢？虽然细菌也可能来自外部环境，但研究者注意到，7种细菌中，有5种是曾被报道的肠道共生菌。难不成它们是从肠道来的？下一步还是要回到CRB1上。CRB1是一种跨膜蛋白，对粘附体连接的完整性至关重要。此前的报道认为CRB1仅在人类和小鼠的眼睛与大脑中表达，但研究者们发现，小鼠结肠细胞顶端也表达CRB1。在缺乏CRB1的情况下，小鼠血-视网膜屏障和结肠上皮屏障都出现了功能障碍，这就为肠菌的眼部大转移提供了机会。当在无菌条件下重新培养Rd8小鼠，研究者发现，Rd8小鼠不再出现视网膜变性；而把它们放回有菌环境，视网膜变性会再次发展。可见，Rd8视网膜变性是高度依赖细菌的。反过来想，如果能够清除细菌，就有希望阻止视网膜变性的进展。研究者给Rd8小鼠施用广谱抗生素，显著减少了视网膜病变的数量和大小，证实抗生素治疗的效果。抗生素治疗显著减少了视网膜变性研究者还使用AAV2载体诱导了Rd8小鼠肠细胞的Crb1表达，这也能有效恢复结肠上皮屏障完整性，减少视网膜变性。许多眼内疾病都与肠菌失调有关，例如葡萄膜炎、青光眼、老年性黄斑变性等，因此近年也出现了肠眼轴的概念。目前对这个概念的假设主要是肠菌或肠菌衍生代谢物激活了视网膜特异性自身反应性T细胞的易位。本研究则提出了新的机制，即活细菌本身的视网膜转移。研究者认为，这一机制可能在其他视网膜变性疾病中存在。参考资料：[1]https://www.cell.com/cell/abstract/S0092-8674(24)00108-9本文作者丨代丝雨

临床研究