Agadagba Stephen K, Liang Ying, Dalton Kristine N, Thompson Benjamin, Yau Suk-Yu
Centre for Eye and Vision Research Limited, Hong Kong Science Park, Hong Kong, China.
School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada.
Front Neurosci. 2025 Apr 25;19:1563607. doi: 10.3389/fnins.2025.1563607. eCollection 2025.
Retinitis pigmentosa (RP) is a progressive retinal degenerative disorder characterized by photoreceptor cell death, leading to vision loss. Current treatments are limited, and there is a need for non-invasive interventions. This study evaluates the neuroprotective effects of voluntary exercise in an RP mouse model and explores the role of the adiponectin signaling pathway in mediating these effects. Pregnant 6 (rd10) mice, a transgenic model of RP, and wild-type C57BL/6J mice were divided into sedentary or voluntary running groups ( per group). Offspring were analyzed at 6 weeks for photoreceptor nuclei counts, outer segment lengths, serum and retinal adiponectin levels, and expression of AMPK and PGC-1α proteins using immunohistochemistry, ELISA, and Western blotting. Voluntary exercise significantly preserved photoreceptor nuclei (97 ± 16 vs. 32 ± 5 in sedentary rd10 mice) and outer segment lengths for rods (13.1 ± 1.2 μ vs. 1.1 ± 0.6 μ) and cones (7 ± 0.9 μ vs. 0.2 ± 0.1 μm) compared to sedentary rd10 mice. Serum adiponectin levels increased significantly in exercised rd10 mice ( < 0.05), while retinal adiponectin levels were elevated in both sedentary and exercised rd10 mice relative to wild-type controls ( < 0.005). No significant changes in AMPK ( = 0.724) and PGC-1α ( = 0.794) protein levels were observed between exercised and sedentary rd10 mice. These findings suggest that voluntary exercise enhances photoreceptor survival in RP by increasing serum adiponectin levels, potentially contributing to neuroprotection. Elevated retinal adiponectin appears linked to RP pathology rather than exercise-induced changes. This study highlights the therapeutic potential of exercise in RP and identifies adiponectin as a promising target for further investigation into neuroprotective mechanisms and treatments.
视网膜色素变性（RP）是一种进行性视网膜退行性疾病，其特征是光感受器细胞死亡，导致视力丧失。目前的治疗方法有限，因此需要非侵入性干预措施。本研究评估了自愿运动对RP小鼠模型的神经保护作用，并探讨了脂联素信号通路在介导这些作用中的作用。将怀孕的6周龄（rd10）小鼠（一种RP转基因模型）和野生型C57BL/6J小鼠分为久坐组或自愿跑步组（每组 ）。在6周龄时分析后代的光感受器细胞核计数、外段长度、血清和视网膜脂联素水平，以及使用免疫组织化学、ELISA和蛋白质免疫印迹法检测AMPK和PGC-1α蛋白的表达。与久坐的rd10小鼠相比，自愿运动显著保留了光感受器细胞核（久坐的rd10小鼠为97±16个，而自愿运动的为32±5个）以及视杆细胞（13.1±1.2μm对1.1±0.6μm）和视锥细胞（7±0.9μm对0.2±0.1μm）的外段长度。运动的rd10小鼠血清脂联素水平显著升高（<0.05），而相对于野生型对照，久坐和运动的rd10小鼠视网膜脂联素水平均升高（<0.005）。在运动和久坐的rd10小鼠之间，未观察到AMPK（P = 0.724）和PGC-1α（P = 0.794）蛋白水平的显著变化。这些发现表明，自愿运动通过增加血清脂联素水平来提高RP中光感受器的存活率，这可能有助于神经保护。视网膜脂联素升高似乎与RP病理相关，而非运动诱导的变化。本研究突出了运动在RP中的治疗潜力，并确定脂联素是进一步研究神经保护机制和治疗方法的一个有前景的靶点。
