GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, Karnataka; Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Department of Paediatric Ophthalmology and Strabismus, Narayana Nethralaya, Bengaluru, Karnataka, India.
Indian J Ophthalmol. 2023 May;71(5):2143-2151. doi: 10.4103/IJO.IJO_3269_22.
Pediatric cataract is a major cause of preventable childhood blindness worldwide. Although genetic mutations or infections have been described in patients, the mechanistic basis of human cataract development remains poorly understood. Therefore, gene expression of structural, developmental, profibrotic, and transcription factors in phenotypically and etiologically distinct forms of pediatric cataracts were evaluated.
This cross-sectional study included 89 pediatric cataract subjects subtyped into 1) prenatal infectious (cytomegalovirus, rubella, and combined cytomegalovirus with rubella infection), 2) prenatal non-infectious, 3) posterior capsular anomalies, 4) postnatal, 5) traumatic, and 6) secondary, and compared to clear, non-cataractous material of eyes with the subluxated lenses. Expression of lens structure-related genes (Aqp-0, HspA4/Hsp70, CrygC), transcription factors (Tdrd7, FoxE3, Maf, Pitx 3) and profibrotic genes (Tgfβ, Bmp7, αSmA, vimentin) in surgically extracted cataract lens material were studied and correlated clinically.
In cataract material, the lens-related gene expression profiles were uniquely associated with phenotype/etiology of different cataracts. Postnatal cataracts showed a significantly altered FoxE3 expression. Low levels of Tdrd7 expression correlated with posterior subcapsular opacity, whereas CrygC correlated significantly with anterior capsular ruptures. The expression of Aqp0 and Maf was elevated in infectious cataracts, particularly in CMV infections, compared to other cataract subtypes. Tgfβ showed significantly low expression in various cataract subtypes, whereas vimentin had elevated gene expression in infectious and prenatal cataracts.
A significant association between lens gene expression patterns in phenotypically and etiologically distinct subtypes of pediatric cataracts suggests regulatory mechanisms in cataractogenesis. The data reveal that cataract formation and presentation is a consequence of altered expression of a complex network of genes.
小儿白内障是全球可预防儿童盲的主要原因。尽管已在患者中描述了基因突变或感染，但人白内障发生的机制基础仍知之甚少。因此，评估了表型和病因学上不同类型的小儿白内障的结构、发育、成纤维增生和转录因子的基因表达。
本横断面研究纳入了 89 名小儿白内障患者，分为 1）产前感染（巨细胞病毒、风疹和巨细胞病毒与风疹联合感染）、2）产前非感染、3）后囊膜异常、4）产后、5）外伤性和 6）继发性白内障，并与眼睛晶状体脱位的透明、非白内障材料进行比较。研究了手术切除白内障晶状体材料中与晶状体结构相关的基因（Aquaporin-0、HspA4/Hsp70、CrygC）、转录因子（Tdrd7、FoxE3、Maf、Pitx3）和成纤维增生基因（Tgfβ、Bmp7、αSmA、Vimentin）的表达，并进行了临床相关性分析。
在白内障材料中，晶状体相关基因表达谱与不同白内障的表型/病因学独特相关。产后白内障的 FoxE3 表达明显改变。Tdrd7 表达水平低与后囊下混浊相关，而 CrygC 与前囊破裂显著相关。与其他白内障亚型相比，Aqp0 和 Maf 在感染性白内障中表达升高，尤其是在 CMV 感染中。Tgfβ 在各种白内障亚型中的表达显著降低，而 Vimentin 在感染性和产前白内障中的基因表达升高。
表型和病因学上不同类型的小儿白内障晶状体基因表达模式之间存在显著相关性，提示白内障发生机制中的调节机制。这些数据表明，白内障的形成和表现是复杂基因网络表达改变的结果。
