Lateral thinking - Interocular symmetry and asymmetry in neurovascular patterning, in health and disease.

No biological system or structure is likely to be perfectly symmetrical, or have identical right and left forms. This review explores the evidence for eye and visual pathway asymmetry, in health and in disease, and attempts to provide guidance for those studying the structure and function of the visual system, where recognition of symmetry or asymmetry may be essential. The principal question with regards to asymmetry is not 'are the eyes the same?', for some degree of asymmetry is pervasive, but 'when are they importantly different?'. Knowing if right and left eyes are 'importantly different' could have significant consequences for deciding whether right or left eyes are included in an analysis or for examining the association between a phenotype and ocular parameter. The presence of significant asymmetry would also have important implications for the design of normative databases of retinal and optic nerve metrics. In this review, we highlight not only the universal presence of asymmetry, but provide evidence that some elements of the visual system are inherently more asymmetric than others, pointing to the need for improved normative data to explain sources of asymmetry and their impact on determining associations with genetic, environmental or health-related factors and ultimately in clinical practice.

RPGR: Its role in photoreceptor physiology, human disease, and future therapies.

Mammalian photoreceptors contain specialised connecting cilia that connect the inner (IS) to the outer segments (OS). Dysfunction of the connecting cilia due to mutations in ciliary proteins are a common cause of the inherited retinal dystrophy retinitis pigmentosa (RP). Mutations affecting the Retinitis Pigmentosa GTPase Regulator (RPGR) protein is one such cause, affecting 10-20% of all people with RP and the majority of those with X-linked RP. RPGR is located in photoreceptor connecting cilia. It interacts with a wide variety of ciliary proteins, but its exact function is unknown. Recently, there have been important advances both in our understanding of RPGR function and towards the development of a therapy. This review summarises the existing literature on human RPGR function and dysfunction, and suggests that RPGR plays a role in the function of the ciliary gate, which controls access of both membrane and soluble proteins to the photoreceptor outer segment. We discuss key models used to investigate and treat RPGR disease and suggest that gene augmentation therapy offers a realistic therapeutic approach, although important questions still remain to be answered, while cell replacement therapy based on retinal progenitor cells represents a more distant prospect.