Investigating Visual Pathway Defects and Mental Health Phenotypes in Albinism through Precision Medicine and Advanced Imaging Techniques

Project Description

Albinism, a genetically heterogeneous disorder, results in hypopigmentation and a range of visual defects, significantly impacting quality of life. Defects in the afferent visual system, particularly abnormal decussation of retinal ganglion nerve fibres at the optic chiasm, are detectable through visual evoked potentials and MRI-based tractography. However, the extent of axonal misrouting in albinism and its relationship with genotype, retinal development, retinal circuitry and functional consequences remains unclear. The University of Leicester (UoL) Ulverscroft Eye Unit (Thomas) has pioneered the use of state-of-the-art optical coherence tomography (OCT) techniques to characterise retinal abnormalities in disorders linked with arrested foveal development. We have also lead an international multi-centre collaboration on foveal development disorders and characterised related disorders such as Foveal Hypoplasia Optic Nerve Decussation Defects with or without Anterior segment dysgenesis (FHONDA). The University of Nottingham (UoN) SPMIC and NIHR BRC Imaging theme (Dineen, Sotiropoulos) provide expertise and cutting-edge diffusion MRI acquisition and analysis platforms for in vivo quantification of retinofugal axonal misrouting and altered whole-brain connectivity, as shown by our previous UoL/UoN collaboration (1-3). We will build on this prior work, employing a precision medicine approach to stratify patients with albinism and related disorders (including FHONDA) based on deep genotyping and phenotyping. We will characterise visual pathway defects across these related disorders providing novel insights into these disorders and the relationship to the clinical phenotypes observed. This includes links to mental health and well-being using questionnaires and association studies (UK Biobank, All of US). The supervisory team has an established track record of training clinical doctoral fellows, providing interdisciplinary expertise in OCT imaging, genetics, neuroimaging, and computational methods.