Jiang Liqin, Dan Yee Shan, Myles William E, Seah Sherlyn H Y, Koh James H Z, Khine Myo Thu, Schmetterer Leopold, Barathi Veluchamy A, Hoang Quan V
Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS, Medical School, Singapore, Singapore.
Department of Ophthalmology, Yong Loo Lin School of Medicine, National, University of Singapore, Singapore, Singapore.
Invest Ophthalmol Vis Sci. 2025 Sep 2;66(12):47. doi: 10.1167/iovs.66.12.47.
To investigate how pigmentation heritage affects susceptibility to form deprivation myopia (FDM) through crossbreeding myopia-susceptible albino and myopia-resistant pigmented guinea pigs (GPs).
Ninety GPs (albino: n = 29, pigmented: n = 29, F1 crossbred: n = 32) were studied. Eye parameters were measured using retinoscopy and A-scan ultrasound. Scotopic electroretinograms were recorded by full-field electroretinography in 36 naive GPs at 1 and 5 weeks of age. Monocular form deprivation (FD) was applied from 1 to 5 weeks of age in 27 GPs, with 27 littermates as controls. The retina, choroid, and sclera were imaged using optical coherence tomography. From control GPs at 5 weeks, scleral melanin was assessed histologically; choroidal melanin and tyrosinase activity in the choroid and sclera were quantified biochemically.
Crossbreds had a pigmented appearance, and choroidal thickness (ChT, 100 ± 19 µm) was thicker than in albino GPs (69 ± 12 µm, P < 0.001) but thinner than in pigmented GPs (124 ± 19 µm, P = 0.004). Choroidal melanin content and tyrosinase activity followed similar patterns and were significantly different (one-way ANOVA): highest in pigmented GPs, intermediate in crossbreds, and undetectable in albinos. Albinos exhibited the largest a-wave amplitudes across the intensity-response functions among the three breeds. Crossbreds displayed a monotonic b-wave intensity-response function, similar to but with higher amplitudes than pigmented GPs, whereas albinos showed a bell-shaped response pattern before the second rise. FD induced significant myopic shift and axial elongation in albinos (spherical equivalent [SE]: -7.83 ± 4.74 D, P = 0.001; axial length [AL]: 0.20 ± 0.14 mm, P = 0.003) and crossbreds (SE: -5.42 ± 2.90 D, P < 0.001; AL: 0.17 ± 0.09 mm, P = 0.001). Pigmented GPs showed a mild myopic shift (-2.08 ± 1.93 D, P = 0.01) with no significant AL changes (0.03 ± 0.08 mm, P = 0.357). FDM severity differed across breeds (SE: P = 0.006, AL: P = 0.004); thicker baseline ChT was associated with less FDM in crossbreds (P = 0.027) and reduced axial elongation in albinos (P = 0.004); retinal and scleral thicknesses were nonpredictive.
Crossbreeding improved retinal function and choroidal morphology, while preserving susceptibility to FDM, suggesting a partial restoration of myopia-inducible mechanisms inherited from the albino lineage. These findings support the value of the crossbred model for investigating retinal and choroidal regulation in myopia.
通过将易患近视的白化豚鼠和抗近视的有色豚鼠杂交，研究色素沉着遗传如何影响形觉剥夺性近视（FDM）的易感性。
研究了90只豚鼠（白化豚鼠：n = 29，有色豚鼠：n = 29，F1杂交种：n = 32）。使用视网膜检影法和A超超声测量眼部参数。在36只新生豚鼠1周龄和5周龄时，通过全视野视网膜电图记录暗视视网膜电图。对27只豚鼠在1至5周龄时进行单眼形觉剥夺（FD），以27只同窝仔作为对照。使用光学相干断层扫描对视网膜、脉络膜和巩膜进行成像。在5周龄时，对对照豚鼠的巩膜黑色素进行组织学评估；对脉络膜和巩膜中的脉络膜黑色素和酪氨酸酶活性进行生化定量分析。
杂交种具有有色外观，脉络膜厚度（ChT，100±19μm）比白化豚鼠（69±12μm，P < 0.001）厚，但比有色豚鼠（124±19μm，P = 0.004）薄。脉络膜黑色素含量和酪氨酸酶活性遵循相似模式，且差异显著（单因素方差分析）：在有色豚鼠中最高，在杂交种中居中，在白化豚鼠中未检测到。在三个品种中，白化豚鼠在强度-反应函数中表现出最大的a波振幅。杂交种呈现单调的b波强度-反应函数，与有色豚鼠相似但振幅更高，而白化豚鼠在第二次上升之前呈现钟形反应模式。FD在白化豚鼠（球镜等效度[SE]：-7.83±4.74 D，P = 0.001；眼轴长度[AL]：0.20±0.14 mm，P = 0.003）和杂交种（SE：-5.42±2.90 D，P < 0.001；AL：0.17±0.09 mm，P = 0.001）中诱导了显著的近视性移位和眼轴伸长。有色豚鼠表现出轻度近视性移位（-2.08±1.93 D，P = 0.01），眼轴无显著变化（0.03±0.08 mm，P = 0.357）。FDM严重程度在不同品种间存在差异（SE：P = 0.006，AL：P = 0.004）；较厚的基线ChT与杂交种中较轻的FDM相关（P = 0.027），并减少了白化豚鼠的眼轴伸长（P = 0.004）；视网膜和巩膜厚度无预测价值。
杂交改善了视网膜功能和脉络膜形态，同时保留了对FDM的易感性，表明从白化豚鼠谱系遗传的近视诱导机制得到了部分恢复。这些发现支持了杂交模型在研究近视中视网膜和脉络膜调节方面的价值。
