- Teresa Iglesias´group at the IIBM uncover new mechanisms linking the brain and visual system, with implications for SINO Syndrome, a rare and poorly understood disease
Today, February 28th, is World Rare Disease Day. This day was established in 2008 with the purpose of raising awareness and helping all people suffering from any rare disease, so that they receive the proper diagnosis and treatment, and thus can lead a better life. What better way to commemorate this day than to present the results recently published by the group of Teresa Iglesias that suppose an approach to know the molecular mechanism of the SINO Syndrome, a disease called "ultrarare".
Research teams led by Teresa Iglesias and Ana Isabel Ramírez, from the Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM) and the Faculty of Optics and Optometry at the Complutense University of Madrid, respectively, have made significant progress in understanding the relationship between hydrocephalus and the visual system. Hydrocephalus is characterized by excessive fluid accumulation in the brain, which can cause neurological damage and visual impairments, particularly in the optic nerve and retina.
This study, published in Fluids and Barriers of the CNS, with Ana Simón-García from Teresa Iglesias’ group as the first author, reveals that changes in certain proteins responsible for regulating water in the brain directly affect the optic nerve and retina.
Among these proteins, Kidins220 stands out as a key molecule for neuronal survival and function. The researchers used a mouse model deficient in the Kidins220 protein, which develops hydrocephalus, as they had previously discovered by the research group at the IIBM. Surprisingly, they found that the absence of this protein did not cause the expected loss of specialized neurons in the retina: “It was surprising to discover that the lack of Kidins220 did not result in the anticipated neuronal damage in the retina,” explains Teresa Iglesias, who first identified this protein in 2000.
“This finding led us to analyse another protein regulated by Kidins220, known as Aquaporin-4 (AQP4), which is crucial for maintaining water balance in the brain. We discovered that the optic nerve exhibited low levels of AQP4, similar to regions of the brain with Kidins220 deficiency, explaining the fluid accumulation in the brain,” continues Teresa Iglesias, who is also a researcher in the CIBER area of Neurodegenerative Diseases (CIBERNED).
However, when studying the retina in these hydrocephalic animals, they observed something unexpected. “We analysed Müller cells, which regulate water balance and nourish retinal neurons, and found higher levels of AQP4. This suggested that the retina may have its own defence mechanisms against changes in water balance, distinct from those of the brain,” highlights Ana Isabel Ramírez.
The importance of this work extends beyond expanding knowledge about the brain-retina relationship. It also offers new insights into the possible mechanisms involved in SINO syndrome (Spastic paraplegia, Intellectual disability, Nystagmus, and Obesity), a rare disease that remains largely unknown to both clinicians and researchers. SINO syndrome affects children, causing motor problems, intellectual disability, obesity, and visual disturbances, in addition to hydrocephalus. This disease, which results from mutations in the KIDINS220 gene, was identified less than ten years ago.
The scientists emphasize the importance of conducting studies in individuals with SINO syndrome using advanced imaging technologies, such as optical coherence tomography (OCT), to examine patients' retinas. OCT is already a routine procedure in many ophthalmology clinics and centres. These analyses could help determine whether different genetic variants in the KIDINS220 gene are associated with specific retinal changes in these patients. “This approach would help us better understand the visual impairments affecting individuals with SINO syndrome and develop new therapies aimed at improving their quality of life,” conclude Drs. Iglesias and Ramírez.
The article, titled: “Kidins220-deficient hydrocephalus mice exhibit altered glial phenotypes and AQP4 differential regulation in the retina and optic nerve, with preserved retinal ganglion cell survival”, is available for download here
The IIBM team led by Teresa Iglesias who have collaborated in this work are: Celia López Menéndez, Luis S. M. Pajuelo, Marina P. Sánchez-Carralero and Marina Sanz in addition to Ana Simón-García as first author.