Caracterización del Sistema del Complemento en la Retinosis Pigmentaria

Retinitis Pigmentosa (RP) represents a heterogeneous group of inherited retinal dystrophies that courses with progressive photoreceptor degeneration and death, leading to visual loss and blindness. This disease is caused by mutations (more than 50) predominantly in photoreceptor-specific genes. Photoreceptor loss progresses with retinal remodelling, microglial recruitment, reactive gliosis and inflammation. Treatment for RP patients is not currently available. The innate immune response is the first line of defence of the organism. The complement system is an effector of this response and plays an essential role in eliminating and clearance of infected and damaged cells. However, it has been shown that elements of the complement system are involved in neurodegenerative disorders contributing to inflammation and synapse loss. In previous studies of our group, we have observed overexpression of complement components in retinas of a mouse model of Retinitis Pigmentosa (rd10). C1q, a component of the classical component pathway, was highly elevated since early stages of the disease. In this work, we have characterized the presence and distribution of C1qa throughout the retina in wild type and rd10 mice. The results showed that C1qa levels were increased in microglial cells in the rd10 retinas respect to the wild type retinas. Besides the microglial expression, we found C1qa deposits in the outer plexiform layer of the retina associated to the synaptic triads formed by photoreceptors and horizontal and bipolar cells. Furthermore, rd10 retinas displayed higher accumulation of C1qa in the synaptic triads than in wild type retinas. Intravitreal injection of a blocking-C1q anti-serum in rd10 mice preserved the visual function compared to control mice, as shown by increased electroretinogram (ERG) a- and b-wave amplitudes. Together, these results indicate that the complement system, particularly C1q, may be involved in the retinal degeneration associated to RP, and that interference with the complement system is a potential therapeutic strategy for the treatment of the disease