TSPO Modulation Prevents Photoreceptor Degeneration and Produces Neuroprotective Effects in an Animal Model of...

The translocator protein (TSPO), an evolutionarily conserved protein located on the outer mitochondrial membrane, is typically expressed at low levels in the central nervous system under normal physiological conditions. However, its expression can increase in response to various pathological conditions, such as neurodegenerative diseases and neuroinflammation. Retinitis pigmentosa (RP) refers to a group of inherited degenerative diseases of the retina; the progression of the pathology is linked to a chronic inflammatory state that leads to the progressive loss of photoreceptors and ultimately to blindness. One of the key processes contributing to the gradual loss of photoreceptors is neuroinflammation, a mechanism in which the TSPO plays a newly studied role. In this context, TSPO could be an excellent target. In the current study, rd10 mice of both sexes were treated with a TSPO ligand, PIGA1138, as an ophthalmic suspension (1 mg/mL) from post-natal day (P)18 to P30, P60, and P90. Retinal function was evaluated through electroretinography, while visual acuity was assessed using the Prusky Water Maze task. Additionally, molecular analyses were performed to assess TSPO expression, alongside examinations of retinal morphology. Results showed significant retinal preservation, reduced photoreceptor loss, and improved retinal responses, suggesting preserved visual function. These findings highlight PIGA1138's potential in mitigating retinal degeneration and preserving function in retinal diseases like RP.