Bennett Lea D, Klein Martin, John Finny T, Radojevic Bojana, Jones Kaylie, Birch David G
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Retina Foundation of the Southwest, Dallas, TX, USA.
Transl Vis Sci Technol. 2020 Apr 23;9(5):14. doi: 10.1167/tvst.9.5.14. eCollection 2020 Apr.
Mutations in the inosine monophosphate dehydrogenase 1 (IMPDH1) gene are a common cause of inherited retinal degeneration (IRD). Due to species- and tissue-dependent expression of IMPDH1, there are no appropriate models of human disease. Therefore, a limited understanding remains of disease expression and rates of progression for IMPDH1-related IRD.
We evaluated semiautomated kinetic and chromatic static perimetry, spectral-domain optical coherence tomography (SD-OCT), and ultra-wide field fundus images with autofluorescence in a cohort of 12 patients (ages 11-58 at first visit). Ten patients had longitudinal data for which rates of progression were estimated.
Visual acuities were relatively stable over time and the photoreceptors within the central retina remained intact. Perifoveal photoreceptor loss measured over a period of years coincided with visual fields, which were constricted and progressed over time in all patients. Rod sensitivity showed a similar pattern of defect to that of the kinetic perimetry and the autofluorescence ultra-wide field imaging. Full-field electroretinograms were severely reduced and the dark-adapted rod and mixed responses were extinguished at earlier visits than the light-adapted cone responses.
There was variability in disease severity at the first visit, but results show that the peripheral retina is more susceptible to the deleterious consequences of an mutation. Given the pattern of degeneration and the alternatively spliced isoforms of , potential interventions may consider targeting the periphery early in disease, modulating transcript expression, and/or preserving central vision at late stages of the disease.
These results inform clinical prognosis and offer evidence strategies toward therapeutic intervention.
肌苷单磷酸脱氢酶1（IMPDH1）基因突变是遗传性视网膜变性（IRD）的常见病因。由于IMPDH1存在物种和组织依赖性表达，因此没有合适的人类疾病模型。因此，对于IMPDH1相关IRD的疾病表现和进展速度仍了解有限。
我们对12例患者（首次就诊时年龄为11 - 58岁）进行了半自动动态和彩色静态视野检查、光谱域光学相干断层扫描（SD - OCT）以及带自发荧光的超广角眼底图像评估。10例患者有纵向数据，据此估计了进展速度。
视力随时间相对稳定，中央视网膜内的光感受器保持完整。多年来测量的中心凹周围光感受器丧失与视野情况相符，所有患者的视野均变窄且随时间进展。视杆细胞敏感性显示出与动态视野检查和自发荧光超广角成像类似的缺陷模式。全视野视网膜电图严重降低，暗适应视杆细胞和混合反应在比明适应视锥细胞反应更早的就诊时就消失了。
首次就诊时疾病严重程度存在差异，但结果表明周边视网膜更容易受到突变的有害影响。鉴于变性模式和IMPDH1的可变剪接异构体，潜在干预措施可考虑在疾病早期针对周边进行治疗，调节转录本表达，和/或在疾病后期保留中心视力。
这些结果为临床预后提供了信息，并为治疗干预提供了策略依据。
