Page 187 - Demo

The eye as a window to the brain1856and that lies within the distal region of the typical 22q11.2 deletion, i.e., within LCR22C-LCR22D, is SNAP29 (synaptosome associated protein 29).44This gene encodes a protein involved in several membrane trafficking steps, and is present in protein complexes that play a role in the subretinal neovascularization of age-related macular degeneration.45, 46 Mice with a loss of function mutation of Snap29 have shown significant thinning of the inner and outer nuclear layers of the retina.47 In addition, excessive mitophagy, responsible for removal of damaged mitochondria, has been suggested to play a role in retinal ganglion cell neurodegeneration.48 This is of interest, since it has also been hypothesized that mitochondrial dysfunction plays an important role in neurodegenerative processes in individuals with 22q11.2DS.49, 50 Thus, the apparent decrease in RNFL (that is formed by axons of ganglion cells) with age in 22q11.2DS, and not in controls, may be indicative of increased mitochondrial dysfunction and axonal damage and may therefore be a potential biomarker for early neurodegeneration in 22q11.2DS. Vascularization of the central nervous system may play a role, but has been scarcely studied in 22q11.2DS. Findings of the few studies include hypoplastic and smaller cerebral arteries,51 thicker cortical veins in patients with migrational disorders (e.g., polymicrogyria), and smaller veins of abnormal number or disorganized appearance.52 Research has also shown elevated cerebral blood flow in the left and right putamen, the right fusiform gyrus, and the left middle temporal gyrus in 22q11.2DS, overlapping with regions of elevated blood flow in patients with idiopathic schizophrenia.53 Increased cerebral blood flow has been found to be positively associated with retinal vascular FD in a cohort of healthy adults aged 65 years and over.54 Another factor that may relate to retinovascular and retinoneural abnormalities is cyanotic congenital heart disease, through a complex interplay of factors including hypoxemia.55Strengths and limitationsThe study provides the first systematic quantitative assessment of retinal morphological features in 22q11.2DS, in a relatively large study sample for a rare disorder. Retinal vascular parameters and retinal layer thickness were assessed using (semi-)automated software, minimizing interrater differences. Limitations of the study include the cross-sectional design and young average age of the study sample. Future longitudinal studies are needed to study changes in retinal vascular parameters and RNFL thickness