Microfluidic isolated human cone photoreceptor progenitors restore visual function in advanced retinal degenerative disease

Inherited retinal diseases (IRDs), such as retinitis pigmentosa, are progressive and currently incurable, leading to retinal degeneration and eventual blindness. These diseases primarily begin with the dysfunction and loss of rod photoreceptors, which subsequently results in the degeneration of cone photoreceptors—critical for central vision and visual acuity. Despite advancements in retinal therapies, no effective cone photoreceptor replacement strategy has been successfully translated into clinical practice. To address this gap, we have developed a novel microfluidic technique for the isolation and enrichment of cone photoreceptors. Using three distinct animal models, we demonstrate the ability of these transplanted cells to engraft and provide neuroprotection, particularly in degenerative models such as rd1 mice and RCS rats. Notably, engrafted cells in rd1 mice formed a functional mosaic pattern in vivo, while scotopic electroretinography (ERG) analysis at 10 weeks post-transplantation in RCS rats confirmed light-responsive activity. These findings provide strong validation for cone photoreceptor replacement therapy, offering a promising therapeutic avenue for conditions such as cone-rod dystrophy and late-stage retinitis pigmentosa.