Identified the role of proinsulin in the maintenance of synapses and vision in retinitis pigmentosa

A study recently published in the journal Cell Death & Disease by researchers Catalina Hernández and Enrique J. de la Rosa, from the Margarita Salas Center for Biological Research, characterizes the role of proinsulin in attenuating synapse and vision alterations in retinitis pigmentosa in mice, supporting its possible therapeutic use in this disease.

Retinitis pigmentosa is a rare disease, although it is the most common cause of hereditary blindness. It is caused by mutations in more than 60 different genes that cause the death of photoreceptors, the cells of the retina that respond to light.

In this work Sánchez-Cruz et al. describe the alterations in the expression and signaling of the insulin receptor in mice with retinitis pigmentosa, demonstrating synaptic disconnection of rod photoreceptors –the cells responsible for vision in dim light conditions– in the early stages of the disease. This synaptic disconnection could be attenuated in a mice model of the disease through the use of gene therapy for the production of proinsulin (the insulin precursor molecule). Additionally, this treatment was able to delay vision loss in mice.

These results highlight the possible therapeutic role of proinsulin in retinitis pigmentosa, perhaps applicable to other types of neurodegeneration.

Reference: Insulin receptor activation by proinsulin preserves synapses and vision in retinitis pigmentosa. Alonso Sánchez-Cruz, Alberto Hernández-Pinto, Concepción Lillo, Carolina Isiegas, Miguel Marchena, Ignacio Lizasoain, Fátima Bosch, Pedro de la Villa, Catalina Hernández-Sánchez & Enrique J. de la Rosa. Cell Death & Disease, volume 13, Article number: 383 (2022).  DOI: 10.1038/s41419-022-04839-0