Zhao He, Wang Hao, Zhang Minfang, Weng Chuanhuang, Liu Yong, Yin Zhengqin
Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China.
Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China.
Front Hum Neurosci. 2023 Jul 18;17:1212398. doi: 10.3389/fnhum.2023.1212398. eCollection 2023.
The pupil light response (PLR) is driven by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to isolate ipRGC-driven pupil responses using chromatic pupillometry and to determine the effect of advanced retinitis pigmentosa (RP) on ipRGC function.
A total of 100 eyes from 67 patients with advanced RP and 18 healthy controls (HCs) were included. Patients were divided into groups according to severity of visual impairment: no light perception (NLP, 9 eyes), light perception (LP, 19 eyes), faint form perception (FFP, 34 eyes), or form perception (FP, 38 eyes). Pupil responses to rod-weighted (487 nm, -1 log cd/m, 1 s), cone-weighted (630 nm, 2 log cd/m, 1 s), and ipRGC-weighted (487 nm, 2 log cd/m, 1 s) stimuli were recorded. ipRGC function was evaluated by the postillumination pupil response (PIPR) and three metrics of pupil kinetics: maximal contraction velocity (MCV), contraction duration, and maximum dilation velocity (MDV).
We found a slow, sustained PLR response to the ipRGC-weighted stimulus in most patients with NLP (8/9), but these patients had no detectable rod- or cone-driven PLR. The ipRGC-driven PLR had an MCV of 0.269 ± 0.150%/s and contraction duration of 2.562 ± 0.902 s, both of which were significantly lower than those of the rod and cone responses. The PIPRs of the RP groups did not decrease compared with those of the HCs group and were even enhanced in the LP group. At advanced stages, ipRGC responses gradually became the main component of the PLR.
Chromatic pupillometry successfully isolated an ipRGC-driven PLR in patients with advanced RP. This PLR remained stable and gradually became the main driver of pupil contraction in more advanced cases of RP. Here, we present baseline data on ipRGC function; we expect these findings to contribute to evaluating and screening candidates for novel therapies.
瞳孔对光反射（PLR）由视杆细胞、视锥细胞和内在光敏性视网膜神经节细胞（ipRGCs）驱动。我们旨在使用彩色瞳孔测量法分离由ipRGCs驱动的瞳孔反应，并确定晚期视网膜色素变性（RP）对ipRGC功能的影响。
纳入67例晚期RP患者的100只眼和18名健康对照（HCs）。根据视力损害的严重程度将患者分为几组：无光感（NLP，9只眼）、光感（LP，19只眼）、微弱形觉（FFP，34只眼）或形觉（FP，38只眼）。记录瞳孔对视杆细胞加权（487 nm，-1 log cd/m²，1 s）、视锥细胞加权（630 nm，2 log cd/m²，1 s）和ipRGC加权（487 nm，2 log cd/m²，1 s）刺激的反应。通过照明后瞳孔反应（PIPR）和瞳孔动力学的三个指标评估ipRGC功能：最大收缩速度（MCV）、收缩持续时间和最大扩张速度（MDV）。
我们发现大多数NLP患者（8/9）对ipRGC加权刺激有缓慢、持续的PLR反应，但这些患者没有可检测到的视杆细胞或视锥细胞驱动的PLR。由ipRGC驱动的PLR的MCV为0.269±0.150%/s，收缩持续时间为2.562±0.902 s，两者均显著低于视杆细胞和视锥细胞反应。与HCs组相比，RP组的PIPR没有降低，甚至在LP组有所增强。在晚期阶段，ipRGC反应逐渐成为PLR的主要组成部分。
彩色瞳孔测量法成功地在晚期RP患者中分离出由ipRGC驱动的PLR。这种PLR保持稳定，并在更晚期的RP病例中逐渐成为瞳孔收缩的主要驱动因素。在此，我们提供了关于ipRGC功能的基线数据；我们期望这些发现有助于评估和筛选新疗法的候选者。
