Mullany Sean, Marshall Henry, Diaz-Torres Santiago, Berry Ella C, Schmidt Joshua M, Thomson Daniel, Qassim Ayub, To Minh-Son, Dimasi David, Kuot Abraham, Knight Lachlan S W, Hollitt Georgina, Kolovos Antonia, Schulz Angela, Lake Stewart, Mills Richard A, Agar Ashish, Galanopoulos Anna, Landers John, Mitchell Paul, Healey Paul R, Graham Stuart L, Hewitt Alex W, Souzeau Emmanuelle, Hassall Mark M, Klebe Sonja, MacGregor Stuart, Gharahkhani Puya, Casson Robert J, Siggs Owen M, Craig Jamie E
Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Ophthalmol Sci. 2022 Apr 19;2(2):100159. doi: 10.1016/j.xops.2022.100159. eCollection 2022 Jun.
To investigate the association between the apolipoprotein E () E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma.
Retrospective analysis of prospective cohort data.
This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which genotypes could be determined.
Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of E4 allele status.
Longitudinal rates of thinning in the macular ganglion cell-inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL).
Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the E4 allele (β = -0.13 μm/year; ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; β = -0.20 μm/year; = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up ( = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 μm vs. 71.9 μm; = 0.011) and pRNFL (77.6 μm vs. 79.2 μm; = 0.045) after a minimum of 3 years of monitoring.
The E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.
在一项针对可疑和早期显性青光眼的队列研究中，调查载脂蛋白E（ApoE）E4痴呆风险等位基因与前瞻性纵向视网膜变薄之间的关联。
对前瞻性队列数据进行回顾性分析。
本研究纳入了参与青光眼进展风险：具有显著关联的相关单核苷酸多态性（PROGRESSA）研究的所有可用眼睛，这些眼睛有可确定ApoE基因型的基因分型数据。
在PROGRESSA研究中确定载脂蛋白E等位基因和基因型，并将其分布与年龄匹配且种族匹配的正常队列——蓝山眼研究进行比较。基于ApoE E4等位基因状态，在PROGRESSA队列中比较使用光谱域光学相干断层扫描（OCT）测量的神经视网膜萎缩的结构参数。
黄斑神经节细胞 - 内丛状层（mGCIPL）复合体和视乳头周围视网膜神经纤维层（pRNFL）的纵向变薄率。
携带≥1个ApoE E4等位基因拷贝的参与者中，mGCIPL复合体变薄率更快（β = -0.13μm/年；P≤0.001）。这一发现在正常眼压性青光眼（NTG）患者的眼中最为明显（β = -0.20μm/年；P = 0.003）。在至少3年的监测后，载脂蛋白E E4等位基因携带者也更有可能失访（P = 0.01），并且平均mGCIPL复合体更薄（70.9μm对71.9μm；P = 0.011），pRNFL也更薄（77.6μm对79.2μm；P = 0.045）。
ApoE E4等位基因与mCGIPL复合体更快的变薄率相关，特别是在NTG患者的眼中。这些结果表明，ApoE E4等位基因可能是青光眼视网膜神经节细胞变性的一个危险因素。
