Voluntary running partially prevents photoreceptor cell death in retinitis pigmentosa

Stephen K. Agadagba ^1* Suk Yu Sonata Yau ^1,2* Kristine Nicole Dalton ^1,3 Benjamin Thompson ^1,3

• ¹ Centre for Eye and Vision Research Limited (CEVR), Hong Kong, Hong Kong, SAR China
• ² Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
• ³ University of Waterloo, Waterloo, Ontario, Canada

Retinitis pigmentosa (RP) is a degenerative eye disease characterized by progressive photoreceptor loss. This study evaluates the neuroprotective effects of voluntary exercise in a mouse model of RP and investigates the role of the adiponectin signaling pathway. We hypothesized that exercise delays photoreceptor degeneration by increasing retinal adiponectin levels, enhancing mitochondrial biogenesis. Pregnant Pde6b rd10 (rd10) mice and wild-type C57BL/6J mice were assigned to voluntary running or sedentary conditions until weaning (n = 46 per group). At six weeks, offspring were analyzed for photoreceptor nuclei count, outer segment lengths, serum/retinal adiponectin levels, and expression of PGC-1α and AMPK proteins. 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 μm vs. 1.1 ± 0.6 μm) and cones (7 ± 0.9 μm vs. 0.2 ± 0.1 μm). However, exercised rd10 mice still exhibited fewer nuclei and shorter rod outer segments than wild-type exercise controls (378 ± 40 nuclei and 23 ± 0.2 μm). Exercise significantly increased serum adiponectin levels in rd10 mice compared to sedentary counterparts (p < 0.05), while retinal adiponectin levels were elevated in both sedentary and exercised rd10 mice relative to wild-type controls (p < 0.005). This suggests that retinal adiponectin elevation is linked to RP pathology rather than exercise-induced changes. No significant differences in PGC-1α (p = 0.724) or AMPK (p = 0.794) protein levels were observed between exercised and sedentary rd10 mice, indicating that the protective effects of exercise may involve alternative mechanisms beyond these pathways. These findings demonstrate that voluntary exercise enhances photoreceptor survival in RP, potentially via increased serum adiponectin levels, while elevated retinal adiponectin may represent a compensatory response to degeneration. 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.